concanavalin-a and Malaria

Malaria and intestinal nematode infection are widespread and co-infection frequently occurs. We investigated whether co-infected intestinal nematodes modulate immunity against co-existing malaria parasites. Infection of C57BL/6 mice with Plasmodium yoelii 17XNL (Py) was transient and self-limiting, but preceding infection with Heligmosomoides polygyrus (Hp), a mouse intestinal nematode, exacerbated malaria resulting in higher parasite burdens and poor survival of the mice. Co-infection with Hp led to reduced Py-responsive proliferation and IFN-gamma production of spleen cells, and higher activation of CD4(+)CD25(+)Foxp3(+) Treg. In vivo depletion of Treg recovered anti-Py immunity and rescued co-infected mice from exacerbated malaria. However, we did not observe any obvious ex vivo activation of Treg by either Hp products or living worms. Our results suggest that intestinal nematodes moderate host immune responses during acute malaria infection by aggressive activation of Treg. Elucidation of the mechanisms of Treg activation in situ is a target for future analyses.

Topics: Animals; Antibodies, Monoclonal; Antigens, Helminth; Cell Count; Concanavalin A; Dendritic Cells; Erythrocytes; Forkhead Transcription Factors; Immune Tolerance; Immunoglobulin G; Interferon-gamma; Interleukin-2 Receptor alpha Subunit; Lymphocyte Activation; Lymphocyte Depletion; Malaria; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Nematospiroides dubius; Parasitemia; Plasmodium yoelii; Spleen; Strongylida Infections; Survival Analysis; T-Lymphocytes, Regulatory

We have previously observed that aged lupus-prone (NZB/NZW)Fl (BWF1) mice when infected with Plasmodium chabaudi show an improvement in their clinical lupus-like symptoms. In order to study the mechanisms involved in the long-lasting protective effect of the P. chabaudi infection in lupus-prone mice we analysed specific aspects of the cellular response, namely the profiles of cytokine mRNA expression and cytokine secretion levels in old BWF1 mice, in comparison with uninfected age-matched BWF1 mice and infected or uninfected BALB/c mice. Two months after infection, cells from BWF1 mice were stimulated with concanavalin A (Con A) and demonstrated a recovery of T cell responsiveness that reached the levels obtained with BALB/c cells. Old BWF1 mice showed high levels of interferon-gamma (IFN-gamma) and IL-5 production and correspondingly low levels of IL-2 and IL-4 secretion before infection with P. chabaudi. Infection did not modify the IFN-gamma levels of BWF1 T cells, whereas it considerably increased the secretion of the Th2-related cytokines IL-4, IL-5 and IL-10. In addition, only BWF1 T cells showed increased mRNA expression of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). This counter-regulatory cytokine network of infected BWF1 mice may be involved in the improvement of their lupus symptoms. The results of our investigations using the complex model of P. chabaudi infection can be extended and, by using more restricted approaches, it may be possible to explain the multiple regulatory defects of lupus-prone mice.

Topics: Animals; Concanavalin A; Crosses, Genetic; Cytokines; Female; Genetic Predisposition to Disease; Immunoglobulins; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphokines; Malaria; Mice; Mice, Inbred BALB C; Mice, Inbred NZB; Plasmodium chabaudi; RNA, Messenger; T-Lymphocytes

In this study, we describe the functional alterations in the host immune system that occur following acute infection with Plasmodium yoelii. Further, we have addressed the question whether the transient condition of altered immune responsiveness can be restored by a cytokine therapy. The lymphoproliferative response towards concanavalin A (Con A) or to cross-linked anti-CD3 mAb was significantly diminished in acutely infected mice compared to immune and normal animals. This condition was associated with poor production of IL-2. In vivo treatment with recombinant IL-2 (rIL-2) resulted in marked diminution of parasitemia (from 24% +/- 6% to 8% +/- 3%) in mice during the acute phase of infection. Despite this diminution in parasitemia, 70% of the IL-2 treated mice died by day 17 post infection. In vivo treatment with rIL-2 led to a partial but significant restoration in lymphoproliferative response to TCR-mediated (cross-linked anti-CD3 mAb) or to Con A-induced stimulation in acutely infected mice. The transcripts for IL-4, IL-5, GM-CSF, and TNF-alpha were expressed in the splenocytes from acutely infected mice not treated with rIL-2. mRNAs for IL-2, IFN-gamma, IL-6, IL-10 which were not detected in acutely infected mice could be reversed by administration of rIL-2 in vivo. We suggest that some of the hyporesponsive T-cells in the acute phase of infection have the potential to be reversed, and this reversal is manifested also at the level of cytokine gene expression.

Topics: Animals; Antilymphocyte Serum; CD3 Complex; Cell Division; Concanavalin A; Female; Gene Expression Regulation; Interferon-gamma; Interleukin-2; Malaria; Mice; Mice, Inbred BALB C; Parasitemia; Plasmodium yoelii; T-Lymphocytes

The expression of selected interleukin receptors by cloned CD4+ T cells specific for the murine malaria parasite Plasmodium chabaudi chabaudi (P. chabaudi) representative of the T-helper (Th) 1 and Th2 subsets was examined. Both sets of clones expressed receptors for those interleukins for which they had a growth factor requirement in vitro. Each Th1 clone expressed receptors for, and was responsive to, interleukin (IL)-2 and IL-4, while each Th2 clone expressed receptors for, and was responsive to, IL-2, IL-4 and IL-1. IL-1 receptor (IL-1R) expression by the Th1 clones was either negligible or could not be detected. The disparity in expression of IL-1R by the Th1 and Th2 clones was more clear-cut than has been previously reported and IL-1R provided a definitive phenotypic marker for clones of the Th2 subset. Should IL-1R expression prove to be a feature of other Th2 cells cultured long-term in vitro, this will be invaluable for investigations involving the phenotyping, depletion or selection of CD4+ T cells of either Th1 or Th2 subset.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Concanavalin A; Epitopes; Interleukin-2; Interleukin-4; Malaria; Mice; Plasmodium chabaudi; Receptors, Interleukin-1; T-Lymphocyte Subsets

We have tested the hypothesis that nitric oxide may be responsible for the immunosuppression reported during malaria infections. We first showed that reactive nitrogen intermediates, which indicate nitric oxide generation, were increased in the plasma of Plasmodium vinckei-infected mice. We next found that Concanavalin A-induced proliferation of spleen cells from these mice was reduced compared with that observed in uninfected animals. The addition of NG-methyl-L-arginine (L-NMMA) for the duration of the cultures restored the malarial proliferative response to normal. We then tested the effect of oral L-NMMA on the proliferative response of P. chabaudi-infected mice to a human red blood cell lysate. The secondary response to this antigen, measured as spleen cell proliferation in vitro ten days after immunization and when there was no discernible parasitaemia, remained normal in L-NMMA-treated P. chabaudi mice, but was decreased in the untreated infected mice. These results suggest a role for nitric oxide in malarial immunosuppression.

Topics: Animals; Arginine; Cell Division; Cells, Cultured; Concanavalin A; Erythrocytes; Humans; Immune Tolerance; Lymphocyte Activation; Malaria; Male; Mice; Mice, Inbred CBA; Nitric Oxide; omega-N-Methylarginine; Plasmodium chabaudi; Spleen

The induction of T helper cell subsets during the course of non-lethal or lethal blood-stage Plasmodium chabaudi AS infection was investigated using inbred strains of mice which differ in the level of resistance to this intraerythrocytic parasite. Resistant C57Bl/6 mice experience a non-lethal course of infection characterized by moderate levels of both parasitaemia and anaemia and resolution of primary acute infection by 4 weeks, while susceptible A/J mice experience lethal infection with fulminant parasitaemia and severe anaemia. T helper subset function was assessed during infection by determining the kinetics of spleen cell production in vitro of the Th1-derived cytokine, interferon-gamma (IFN-gamma), and of the Th2-derived cytokine, IL-5, using sandwich ELISAs. Spleen cells from resistant C57Bl/6 mice were found to produce high levels of IFN-gamma within 1 week of infection in response to both the mitogen concanavalin A (Con A) and malaria antigen. Furthermore, CD4+ T cells were found to be the source of IFN-gamma while both CD4+ and CD8+ T cells were found to produce IL-5. Decreased IFN-gamma production after day 10 was concomitant with significant production of IL-5 between 2 and 3 weeks post infection. In contrast, spleen cells from susceptible A/J mice produced high levels of IL-5 within the first week of infection. In addition, these animals were found to have high serum levels of IL-5. These results, thus, confirm previous observations that resolution of primary blood-stage P. chabaudi infection occurs by sequential activation of Th1 CD4+ T cells followed by activation of the Th2 subset, and in addition, suggest that induction of a strong Th2 response early in infection may lead to a severe and lethal course of malaria.

Topics: Animals; Antigens, Surface; CD8 Antigens; Cells, Cultured; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Immunity, Innate; Interferon-gamma; Interleukin-5; Kinetics; Lymphocyte Activation; Lymphocyte Depletion; Malaria; Membrane Glycoproteins; Mice; Mice, Inbred A; Mice, Inbred C57BL; Nerve Tissue Proteins; Plasmodium chabaudi; Spleen; T-Lymphocytes, Helper-Inducer; Thy-1 Antigens; Time Factors

This study investigates the effects of the male sex hormone, testosterone (Te), on self-healing of Plasmodium chabaudi malaria as well as on protein expression and functional properties of total spleen cells and splenic T cells in females of the mouse strain C57BL/10. About 90% of the B10 females survive a challenge with 10(6) P. chabaudi-infected erythrocytes. The percentage of self-healers, however, is reduced to about 60%, 40%, and 0% after pretreatment with Te for 1, 2, and 3 weeks, respectively. The progressive loss of the capability of self-healing is correlated with an increasing expression of five proteins in splenic non-T cells as revealed by two-dimensional fluorography after metabolic labelling of total spleen cells and T cells with [35S]methionine. These have molecular masses (isoelectric points) of about 10 kDa (pI 5.7), 14 kDa (pI 6.3), 14 kDa (pI 6.4), 38 kDa (pI 6.5), and 46 kDa (pI 5.5), respectively. Splenic non-T cells from mice treated with Te for 3 weeks have gained an increased capability to stimulate the concanavalin A-induced proliferative response of T cells. Te induces the changes in functional properties and protein expression of splenic non-T cells only in vivo and not in vitro. This suggests that the changes in splenic non-T cells as well as the prevention of self-healing P. chabaudi malaria are not directly induced by Te but rather indirectly, i.e. by a Te metabolite and/or Te-induced factor(s).

Topics: Animals; Cell Division; Concanavalin A; Disease Susceptibility; Electrophoresis, Gel, Two-Dimensional; Female; Malaria; Mice; Mice, Inbred C57BL; Plasmodium chabaudi; Protein Biosynthesis; Spleen; T-Lymphocytes; Testosterone

Serum pools from mice undergoing lethal infection with Plasmodium berghei inhibit the growth of an IL2-dependent mouse cytotoxic T cell line (CTLL). A partially purified preparation of the inhibitory factor specifically inhibited IL2-mediated events such as IL2-dependent CTLL growth and the Con A mitogenic response of normal mouse spleen cells. Production of and response to IL1, as well as growth of myeloma lines, was not affected. Administration of the partially purified preparation to normal mice resulted in a significant depression in IL2 production, thereby indicating a role for the inhibitory factor in maintaining immune depression in malaria-infected mice.

Topics: Animals; Cell Division; Concanavalin A; Female; Interleukin-1; Interleukin-2; Lymphocyte Activation; Malaria; Mice; Mice, Inbred BALB C; Plasmodium berghei; Receptors, Interleukin-2; T-Lymphocytes, Cytotoxic

The peripheral blood lymphocyte response to affinity purified soluble Plasmodium falciparum antigens from in vitro cultures was studied in seven patients with acute falciparum malaria, on eight occasions, and in 15 persons having had malaria, at various times post infection, on 24 occasions. During infection, the response was low or absent in most patients (median stimulating index = [SI] = 1.4). One week post infection, a specific antigen response rose (SI = 2.9), but not to the levels found two weeks to one year post infection (SI = 5.8). At two to four years post infection, it was still present. During a recrudescence of malaria in a single patient, it was lost temporarily. The response to optimal concentrations of lectin mitogens and to tuberculin antigen was not suppressed in acute malaria.

Topics: Adult; Antigens, Protozoan; Concanavalin A; Female; Humans; Lymphocyte Activation; Malaria; Male; Phytohemagglutinins; Plasmodium falciparum; Pokeweed Mitogens; Time Factors; Tuberculin

Interleukin 1 (I1-1) produced by activated macrophages and interleukin 2 (I1-2) released by a subset of T lymphocytes upon antigen or mitogen stimulation are the soluble mediators involved in the mechanism of T-cell activation, proliferation, and differentiation. Since these T-cell responses are depressed during malaria infection, the capacity of macrophages to produce I1-1 following lipopolysaccharide (LPS) stimulation and that of lymphocytes to release I1-2 upon stimulation with concanavalin A (Con-A) in mice infected with either nonlethal Plasmodium yoelii (NLPY) or lethal Plasmodium berghei (PB) malaria parasites was analyzed. The results show that while adherent cells from spleen or peritoneal exudates of infected mice were able to produce I1-1, although to a different extent in the two infections, splenic lymphocytes were unable to produce I1-2, but capable of responding to it. This suggests that the diminished T-cell responses in malaria might be due to a defect of I1-2 synthesis.

Topics: Animals; Concanavalin A; Female; Indomethacin; Interleukin-1; Interleukin-2; Kinetics; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Macrophage Activation; Macrophages; Malaria; Mice; Mice, Nude; Spleen; T-Lymphocytes

Antigen specific and concanavalin A (Con A)-induced lymphocyte blastogenesis responses were monitored in the spleens of rats infected with Plasmodium berghei. Con A responses were depressed only at the time of peak parasitaemia. The antigen specific blastogenesis response was either not in evidence, or at a low level during the periods of patent or subpatent infection (up to 8 weeks after infection). Higher levels of blastogenesis were seen from 8 to 12 weeks after infection, which correlates with clearance of subpatent infection. Fractionation of immune spleen cell suspensions on nylon wool columns indicated that purified T cells did not respond to parasite antigen.

Topics: Animals; Antigens; Cell Separation; Concanavalin A; Lymphocyte Activation; Malaria; Male; Plasmodium berghei; Rats; Rats, Inbred Strains; Spleen; T-Lymphocytes

Con A-pretreated mononuclear (MNC) cells from Thai adults with naturally acquired P. falciparum or P. vivax malaria were significantly less effective in suppressing the responsiveness of autologous or normal allogeneic responder cells to mitogenic lectins or allogenic stimulator cells than pretreated cells from healthy donors. Serial studies of three patients demonstrated that reduced suppressor cell activity was present early in malaria infection but returned to normal soon after treatment. These studies demonstrate that the loss of T cells previously observed in patients with malaria, in part may functionally represent a loss of suppressor T cells.

Topics: Adult; Concanavalin A; Humans; Lymphocyte Culture Test, Mixed; Malaria; Male; Phytohemagglutinins; Plasmodium falciparum; Plasmodium vivax; T-Lymphocytes, Regulatory; Thailand

Studies were initiated to determine whether or not transformation of lymphocytes isolated from individuals functionally immune to malaria would be a useful tool for the identification of protective antigens derived from continuous cultures of Plasmodium falciparum. Soluble antigen preparations stimulated lymphoproliferative responses in cells isolated from immune and nonimmune individuals. To rule out the possibility that those nonspecific responses were mixed lymphocyte reactions or other, undefined stimuli due to the heterologous nature of the lymphocyte culture system, subsequent experiments were conducted using extracts from parasites cultured in erythrocytes obtained from the same donors whose lymphocytes were tested. Soluble parasite extracts from continuously cultured P. falciparum produce nonspecific lymphocyte blast transformation responses in immunologically naive individuals. Such mitogens should be identified and removed from antigen preparations before a vaccine against malaria can be developed.

Topics: Animals; Antigens; Cell Survival; Concanavalin A; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Malaria; Plasmodium falciparum

Topics: Adjuvants, Immunologic; Animals; Antibody-Producing Cells; Antilymphocyte Serum; Clone Cells; Concanavalin A; Female; Graft vs Host Reaction; Horses; Immunoglobulins; Malaria; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Phytohemagglutinins; Rabbits; Sheep; T-Lymphocytes

The binding of normal and Plasmodium falciparum-infected squirrel monkey erythrocytes to columns of ligand-coated agarose beads was compared. Concanavalin A, ricin, soybean and peanut agglutinin-coated beads retain erythrocytes containing large developmental stages of the parasite preferentially to ring-containing erythrocytes or to normal erythrocytes. Binding is inhibited by the sugar corresponding to the lectin's specificity. Preferential binding does not occur with wheat germ or Ulex europaeus agglutinin-coated beads. When infected blood is preincubated in immune serum, infected erythrocytes are specifically retained by Protein A-coated beads. These peculiar binding properties reflect modifications of the infected erythrocyte membrane.

Topics: Agglutinins; Animals; Chromatography, Affinity; Concanavalin A; Erythrocytes; Lectins; Malaria; Plasmodium falciparum; Polysaccharides; Saimiri; Sepharose; Staphylococcal Protein A

The immune response of splenic cells to SRBC and LPS or Con A mitogens is suppressed in P. chabaudi-infected mice. When mixed with cells from normal donors, spleen cells from infected mice also suppressed anti-SRBC and mitogenic responses. Suppression was not detected in lymph node cells, bone marrow, or thymocytes from infected mice. Removal of infected red cells had no effect on suppression. The cell population responsible for the suppressive activity was adherent to plastic, resistant to irradiation and anti-Thy-1 plus complement treatment.

Topics: Animals; Antibody Formation; Cell Adhesion; Concanavalin A; Erythrocytes; Female; Hemolytic Plaque Technique; Immunosuppression Therapy; Lipopolysaccharides; Malaria; Mice; Plasmodium; Sheep; Spleen

MALARIA RESULTS IN TWO SEEMINGLY PARADOXICAL PERTURBATIONS OF THE IMMUNE RESPONSE: polyclonal B-cell activation and immunosuppression. To determine what immunoregulatory role mediators secreted by adherent cells might play in these alterations, we cultured adherent cells from uninfected mice and from mice at different times during infection with Plasmodium berghei or P. yoelii. Culture supernatants obtained from these cells were tested for their ability to enhance the in vitro proliferative responses of thymocytes to suboptimal concentrations of concanavalin A or to inhibit the mitogen-stimulated proliferation of normal spleen cells. Supernatants obtained from adherent cells of mice early in infection (days 1 to 3) contained significantly elevated levels of enhancing activity which on Bio-Gel P-100 chromatography resembled lymphocyte-activating factor. Later in infection (days 4 and 5), these supernatants contained inhibitory activity. Normal adherent cells, when cocultivated in vitro with parasitized erythrocytes, ingested parasite debris and were stimulated to produce the enhancing factor. At high parasite/adherent-cell ratios, cells elaborated an inhibitory factor. These findings suggest that during malaria, adherent cells are converted from a nonspecific helper role to a nonspecific suppressor role. This modulation in function may be due to the direct interaction between adherent cells and parasitized erythrocytes.

Topics: Animals; Cell Adhesion; Concanavalin A; Immunosuppression Therapy; Lymphocyte Activation; Macrophages; Malaria; Male; Mice; Plasmodium

The response of spleen and peripheral blood lymphocytes (PBL) to mitogen stimulation with phytohemagglutinin (PHA), Concanavalin A (ConA), and pokeweed mitogen (PWM) was determined for owl monkeys (Aotus trivirgatus) experimentally infected with the Vietnam-Oak Knoll (FVO) and the Uganda-Palo Alto (FUP) strains of Plasmodium falciparum. PBL from Panamanian Aotus monkeys with less than 25% FVO infection responded normally to mitogen stimulation; however, increased parasitemia of 25--50% resulted in a significant suppression of ConA responsiveness. Colombian Aotus monkeys infected with the PUF strain also developed a suppression to ConA stimulation but with a lower parasitemia (10--25%). When the parasitemia became greater than 50% in these animals, PHA, ConA, and PWM responses were significantly decreased in cultures of PBL. Spleen cells from all acutely infected Aotus monkeys were suppressed to PHA and ConA, but not PWM stimulation. Changes in mitogen responsiveness of experimentally infected Aotus monkeys are similar to those reported for humans with acute falciparum malaria.

Topics: Animals; Aotus trivirgatus; Concanavalin A; Haplorhini; In Vitro Techniques; Lectins; Lymphocytes; Malaria; Mitogens; Plasmodium falciparum; Spleen

Plasma collected from owl monkeys during the acute phase of Plasmodium falciparum infection was shown to adversely affect several in vitro responses which are considered to be correlates of cell-mediated immune functions of normal monkeys. In the presence of acute-phase plasma, response of normal monkey peripheral blood lymphocytes to stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen was severely reduced, as was the ability of peripheral blood lymphocytes to respond to allogenic and xenogenic histocompatible antigens. The transformation response of peripheral blood lymphocytes from normal humans to phytohemagglutinin and concanavalin A was also suppressed. Since acute-phase plasma was not cytotoxic for peripheral blood lymphocytes, decreased responsiveness did not result from cell destruction. Acute-phase plasma appears to block initial steps in lymphocyte transformation.

Topics: Animals; Aotus trivirgatus; Concanavalin A; Haplorhini; Lymphocyte Activation; Malaria; Phytohemagglutinins; Plasma; Pokeweed Mitogens

Topics: Adjuvants, Immunologic; Animals; Babesia; Blood; Concanavalin A; Diethylstilbestrol; Erythrocytes; Escherichia coli; Female; Injections, Intraperitoneal; Lipopolysaccharides; Malaria; Male; Mice; Plasmodium; Plasmodium berghei; Poly A-U; Polysaccharides, Bacterial; Propionibacterium acnes; Reticulocytes

The reaction of spleen cells from rats infected with Plasmodium berghei to non-specific mitogens has been measured. The cells have been stimulated in vitro by phytohaemagglutinin, concanavalin-A and by bacterial lypopolysaccharide. In addition the release of lymphocyte activating factor (LAF) by splenic macrophages has been assayed using a heterologous thymocyte culture. The reactivity of spleen lymphocytes from malarious rats is severly affected. The cells do not react either to the T cell-specific mitogens or to the B-cell stimulant. The reactivity of macrophages, as measured by the release of LAF, was not altered by the disease.

Topics: Animals; Cell Adhesion; Concanavalin A; Lectins; Lipopolysaccharides; Lymphocyte Activation; Macrophages; Malaria; Male; Plasmodium berghei; Rats; Rats, Inbred Lew; Spleen

Concanavalin A (Con A) injected intraperitoneally at a dose of 50 mg per kg was not lethal for male BALB/c mice. Six hours after administration of 5 mg Con A/kg, the proportioy 24 hr, the proportion of granulocytes had decreased to 56%. Adiministration of 5 mg Con A/kg 24 hr before 200 mg of 5[3,3-bis(2-chloroethyl)-triazeno]-imidazole-4-carboxamide per kg, or 100 mg of 5-fluorouracil per kg resulted in a significant enhancement of lethality. Simulatenous administration of 5 mg Con A/gm and 10 mg of daunomycin per kg also resulted in enhanced lethality. Administration of 5 mg Con A/kg 24 hr before 40 mg of 1,3-bis(2-chloroethyl)-1-nitrosourea per kg, 200 mg of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea per kg, 1000 mg of cytosine arabinoside per kg, 0.1 mg of mithramycin per kg, 2 mg of pactamycin per kg or 1 mg of vincristine per kg did not result in enhanced lethality. Lipid A prepared from Escherichia coli 0127:B8 Boivin lipopolysaccharide has been complexed to Con A. The lipid A-Con A complex (5mg/kg) was no more, or less effective in enhancing the lethality of 5-fluorouracil than 2.5 mg Con A/kg. The lipid A-Con A complex (40 mg/kg), given simultaneously with drug, enhanced lethality per kg. In this regard, the lipid A-Con A complex had vincristine per kg. In this regard, the lipid A-Con A complex had activity comparable to the complex formed between lipid A and bovine serum albumin. Conceivably, Con A can be used to enhance the susceptibility of neoplastic cells to phase-specific antitumor drugs, especially those acting on deoxyribonucleic acid synthesis.

Topics: Animals; Antineoplastic Agents; Concanavalin A; Cyclic AMP; Drug Synergism; Granulocytes; Leukocyte Count; Liver; Lung Neoplasms; Malaria; Male; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Plasmodium berghei

Chloroquine increases the inhibition of cultured lymphocytes by high concentrations of phytohemagglutinin (PHA) or concanavalin A (Con A). The inhibition is also increased by complement. Thus chloroquine and complement have similar effects. Time-course studies show that chloroquine increases the rate of onset of the complement-dependent inhibition. In serum preheated to inactivate complement, chloroquine can partially simulate the effect of complement. It is suggested that at certain stages in malaria or autoimmune disease the rate of clearance of parasitized erythrocytes or autoreactive lymphocytes is limited by the concentration of complement. Under these conditions a drug such as chloroquine, which could enhance or simulate the action of complement, might be of therapeutic value.

Topics: Animals; Autoimmune Diseases; Cells, Cultured; Chloroquine; Complement System Proteins; Concanavalin A; Dose-Response Relationship, Drug; Female; Hot Temperature; Humans; Lectins; Lymphocyte Activation; Lymphocytes; Malaria; Rats