inosine-pranobex and Burns

The remarkable progress achieved in control of infections in burned patients has significantly increased survival rates. Nevertheless, septic complications are still the leading cause of death in these patients. The immunologic disturbances present after severe burns certainly play a key role in susceptibility to infection, and in particular the impairments of the phagocytic system warrant major investigative efforts in order to increase host defenses. Determination of phagocytic and microbicidal capacity of neutrophils from burned patients evidenced a marked functional impairment of these cells. The alterations recorded were partly due to intrinsic (cellular) defects, and partly to extrinsic (serum) defects. Indeed, opsonic factors are known to be reduced in these patients, but also phagocytosis-inhibiting factors such as immunocomplexes have been detected in the patients we have studied. Administration of the immunomodulating agents methysoprinol and timostimoline were found to be effective in partially restoring neutrophil function. Rational immunotherapy in burned patients will consist of replacement of humoral mediators, clearance of inhibitory factors and stimulation of the cellular effectors of immunity.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Bacterial Infections; Burns; Child; Clinical Trials as Topic; Fibronectins; Humans; Immune Tolerance; Inosine; Inosine Pranobex; Lymphocytes; Middle Aged; Neutrophils; Phagocytosis; Thymus Extracts; Time Factors

The effect of in vivo administration of Isoprinosine (ISO) on, i) the proliferation of splenic lymphocytes in response to the T-cell mitogen, concanavalin-A (Con-A) and, ii) the natural killer (NK) cell cytotoxicity was studied following a full skin thickness burn injury in a rat model. Administration of ISO (100 mg/kg body wt/day) twice daily, resulted in significant augmentation of the proliferative responses of lymphocytes compared to non-treated burned animals, at 7 days post injury. However, it did not effect the lymphoproliferation at 14 days post injury, the time period at which a complete suppression of lymphocyte proliferation was observed in burned non-treated animals. Also, the proliferation of lymphocytes from normal nonburned animals was not affected by treatment with ISO. ISO treatment of the burned animals resulted in a significant increase in the NK cytotoxicity compared to non-treated burned animals. As with Con-A responses, ISO administered to control nonburned animals did not have any effect on NK cell cytotoxicity. Our studies thus indicate that ISO can be a potential immunomodulator of suppressed immune function following thermal injury, particularly in patients whose lymphocyte responses to T cell mitogen Con-A are not completely suppressed.

Topics: Adjuvants, Immunologic; Animals; Burns; Concanavalin A; Inosine; Inosine Pranobex; Killer Cells, Natural; Lymphocyte Activation; Rats; Rats, Inbred Strains; Time Factors

Patients with various conditions associated with immunologic deficiency (cancer, radiotherapy, surgery, burns, aging, prodromal Acquired Immunodeficiency Syndrome, were treated with inosiplex (INPX) at a dose of 3-4 g/day for periods of time ranging from 1 week to several months. Patients were evaluated clinically, and immunologically with the following assays; natural killer (NK) cytotoxicity, T-lymphocyte count, mitogen-induced proliferation, E rosettes, and skin test reactivity. The data resulting from this large and varied population were quite consistent and reproducible, and indicated that INPX treatment was effective in simultaneously reducing the incidence of complications, infections and mortality while enhancing the immune status of the patient. It has therefore been concluded that an immunopharmacologically active agent such as INPX can elicit important clinical benefits in patients with disorders of diverse etiology, perhaps through modulation of an immunologic defect that is common to a variety of seemingly unrelated conditions.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Antineoplastic Agents; Burns; Humans; Immunity; Immunologic Deficiency Syndromes; Inosine; Inosine Pranobex; Kinetics; Middle Aged; Models, Biological; Neoplasms; Postoperative Complications

A series of experiments has been performed in order to evaluate the effects of methisoprinol on immune response following thermal injury. Methisoprinol treatment induced a sharp stimulation of the cell-mediated immune response in burned animals. This finding demonstrates that methisoprinol may be useful in burns to prevent infections related to immune depression.

Topics: Animals; Antibody Formation; Burns; Female; Guinea Pigs; Immunity, Cellular; Inosine; Inosine Pranobex; Male