concanavalin-a and Drug-Hypersensitivity

Topics: Concanavalin A; Drug Hypersensitivity; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Phytohemagglutinins; T-Lymphocytes

Immune-mediated drug hypersensitivity is a particularly concerning health-safety issue among clinicians given its unpredictability and potentially life-threatening effects, especially with exposure to intravenous drugs. Therefore, the development of intravenous drug-exposure models for drug-hazard assessments has garnered increasing interest in recent years. In this study, we used reporter antigens popliteal lymph node assay to investigate the potential value of intravenous exposure to a selected variety of allergenic compounds, including ovalbumin (OVA), concanavalin A (ConA) and diclofenac. The trinitrophenyl (TNP)-specific antibody-forming cells were used to assess the systemic immune responses to a bystander antigen. Mice were subsequently sensitized by TNP-OVA, and then intravenous exposure to one of the selective compounds. As expected, all positive compounds induced significant popliteal lymph node (PLN) proliferation compared with the control. OVA significantly increased Cluster of Differentiation 4 receptors (CD⁴)⁺ interleukin-4 (IL-4)⁺ T-helper 2 (Th2) cells and, consequently, increased the ratios of IL-4/interferon-γ (IFN-γ) antibody-forming cells (AFCs) in PLNs, while bringing about a dose-dependent increase in immunoglobulin G1 (IgG1) AFCs; these findings indicate that a Th2 hypersensitivity response was induced. A Th2 response was also observed in diclofenac sodium-treated groups, and for ConA, a more mixed Th1/Th2 immune response appeared to be induced. In addition, there was no marked reaction with the negative compound. Together, it seems likely that the intravenous exposure model may be useful for drug-induced systemic hypersensitivity assessments.

Topics: Adjuvants, Immunologic; Allergens; Animals; Antigen-Antibody Reactions; Antigens; Cell Proliferation; Concanavalin A; Diclofenac; Drug Hypersensitivity; Female; Injections, Intravenous; Local Lymph Node Assay; Lymph Nodes; Mice; Mice, Inbred BALB C; Ovalbumin; Risk Assessment; Trinitrobenzenes

Cutaneous insulin allergy remains a clinical problem despite the use of highly purified human insulins. We used in vitro lymphocyte-transformation studies to examine the reactivity of various insulin formulations in diabetic patients with (n = 4) and without (n = 8) cutaneous allergies. Nonspecific response to concanavalin A demonstrated a greater than 40-fold response in both groups. Control patients did not respond to the addition of commercial insulin preparations (stimulation index [SI] less than 4), whereas allergic patients had an 11-fold response to beef (P less than 0.01), a 10-fold response to pork (P less than 0.01), and a 6-fold response to human (P less than 0.01) insulins. This response was limited to a single insulin manufacturer's preparations and was uniform in all three species tested. Efforts to identify the offending agent revealed no lymphoblast transformation when crystalline insulin was used or when commercial preparations were purified to a single peak by high-performance liquid chromatography (HPLC). Pure crystalline insulin dimers of beef, pork, and human species were tested; control subjects responded with mean SIs of 1.9, 1.9, and 1.8, respectively, whereas allergic patients showed greater reactivity to beef (SI 7.3) and pork (SI 14.8). The lymphoblast-transformation response to crystalline human dimer was dose dependent with mean SIs of 0.9 at low concentration (2.8 ng/ml) and 19.2 at a higher concentration (20.4 ng/ml). The commercial insulin preparations were run on size-exclusion HPLC to determine high-molecular-weight aggregate content. Independent of species, a single manufacturer had products demonstrating aggregate levels 3- to 6-fold higher than those found in other manufacturers' preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Concanavalin A; Drug Hypersensitivity; Humans; Immunochemistry; Insulin; Lymphocyte Activation; Molecular Weight; Skin

To evaluate the specificity of the lymphocyte transformation test (LTT) in the diagnosis of drug allergy we studied over 71 days an atopic woman with a past history of frequent adverse reactions to pyrazolone drugs. Rechallenge with the incriminated substances aminophenazone (aminopyrine) and propyphenazone was carried out on Days 11 and 31 respectively. An immediate type of hypersensitivity reaction was seen after 100 mg aminophenazone, while 100 mg of propyphanozone led to a serum sickness-like syndrome. We found two specifically sensitized lymphocyte populations using either the pure substance or sera containing metabolite in cell cultures. Stimulatory responses with indices ranging between 3 and 6 were seen 3-4 days after exposure, and the tests remained positive in both instances for 3-4 weeks. Specific sensitization was proven by positive skin tests and by a small but distinct lymphocyte proliferative response before challenge. Several lymphocyte function tests were performed over a period of 53 days and revealed a large fall in pokeweed mitogen-induced immunoglobulin synthesis and an increase in suppressor cell activity after rechallenge with aminophenazone. We conclude that the proliferative response observed in the presence of the offending drug is due to the activation of T memory cells and therefore highly suggestive of a true allergic reaction.

Topics: Adult; Aminopyrine; Anti-Inflammatory Agents, Non-Steroidal; Antipyrine; Concanavalin A; Drug Hypersensitivity; Humans; Immunoglobulin G; Lymphocyte Activation; Male; Mitogens; Pyrazoles; Rhinitis, Allergic, Perennial; Time Factors

Topics: Candida; Child; Concanavalin A; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Humans; Lymphocyte Activation; Phenytoin; Phytohemagglutinins; Pokeweed Mitogens; Seizures

Topics: Animals; Chromatography, Affinity; Concanavalin A; Drug Hypersensitivity; Haptens; Immunity, Maternally-Acquired; Immunization, Passive; Immunosuppression Therapy; Methylmannosides; Mice; Mice, Inbred CBA; Picryl Chloride; T-Lymphocytes; Trinitrobenzenesulfonic Acid

This study compared the responses of CFW and CFI mice to concanavalin A (con A) and the histamine-sensitizing factor (HSF) of Bordetella pertussis. There were marked similarities between these two agents with regard to systems implicated in induced histamine sensitivity. Con A, like HSF, induces the sensitivity in CFW but not in CFI mice. The sensitizing agents both require the same time for optimum sensitization, both induce cutaneous sensitivities to histamine, and the mice are protected from the induced susceptibility of both agents by epinephrine and by desensitization with serotonin. They differed in that con A did not induce the systemic susceptibility to serotonin or to combined histamine and serotonin which is produced by HSF. The major difference related to mechanisms of action was the failure of con A to induce a systemic beta-adrenergic blockade, the block of which is manifested in HSF-treated CFW and CFI mice by the inhibition of an epinephrine-induced hyperglycemia. The resistance of beta-blocked CFI mice to histamine, and the susceptibility to histamine of the unblocked CFW mice sensitized with con A, is inconsistent with the theory that susceptibility results from a systemic adrenergic imbalance, but does not preclude a local adrenergic effect as the common element in histamine-sensitizing agents.

Topics: Animals; Concanavalin A; Drug Hypersensitivity; Drug Synergism; Female; Histamine; Mice; Mice, Inbred Strains; Serotonin