concanavalin-a and Critical-Illness

To test propofol lipid emulsion formulation for its immunosuppressive effects.. Propofol lipid emulsion and the emulsion alone were tested at increasing concentrations and compared to initial values and between each other. Propofol alone could not be tested due to its insolubility into the culture medium.. Lymphocytes from 12 surgical intensive care (ICU) patients (median APACHE score 16 and median TISS score 28) and 12 healthy volunteers.. Phytohaemagglutinin-, concanavalin A- and pokeweed mitogen-induced lymphocyte proliferative responses were measured in the presence of increasing concentrations of propofol lipid emulsion formulation or the lipid emulsion.. Lymphocyte proliferative responses from ICU patients were in general on a lower level than in the volunteers. The propofol lipid emulsion formulation (Diprivan) decreased pokeweed mitogen-induced proliferative responses of lymphocytes from ICU patients at propofol concentrations found in the circulation (1-10 micrograms/ml) and the lipid emulsion alon at 100 micrograms/ml triglyceride concentrations while the other mitogen-induced responses were not affected. No changes were observed in the mitogen-induced responses of lymphocytes from healthy volunteers.. Propofol emulsion formulation decreased in surgical intensive care patients pokeweed mitogen-induced lymphocytic responses in vitro at clinically found concentrations, indicating the need for further studies to test B-lymphocyte functions and T-B-lymphocyte co-operation during propofol lipid emulsion administration. (ICU) patients is widespread because of its good control of sedation. Propofol is currently administered in fat emulsion which is considered immunosuppressive during bolus injection or rapid infusion. Therefore, effects of a propofol fat emulsion formulation on proliferative responses of lymphocytes were studied in blood samples obtained from healthy volunteers and ICU patients known to be immunosuppressed.

Topics: Adolescent; Adult; Aged; B-Lymphocytes; Chemistry, Pharmaceutical; Concanavalin A; Critical Illness; Dose-Response Relationship, Drug; Fat Emulsions, Intravenous; Humans; Immunocompromised Host; Intensive Care Units; Lymphocyte Activation; Lymphocytes; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Propofol; Severity of Illness Index; Trauma Severity Indices

Dopamine is currently used in the ICU for its vasopressor, renal vasodilating, and cardiac inotropic properties. Animal studies have shown both endocrine and T-lymphocyte alterations with dopamine agonist administration. The relationships between exogenous dopamine and patient hormonal and lymphocyte proliferative responses have not been evaluated in the critically ill patient. These findings furnished the impetus for the present study.. Prospective, controlled, clinical study.. All patients admitted to the ICU at Truman Medical Center were evaluated for admission into the protocol, excluding patients whose medications or diseases produced effects in the study-dependent variables. Before institution of dopamine therapy, blood samples were taken for T-cell analysis and prolactin measurement. Daily, early morning blood samples were taken if the dopamine infusion was > 5 micrograms/kg/min for 4 hrs during that 24-hr period. An early morning postdopamine sample was taken on the first day after dosage discontinuation. Control blood samples for determination of T-cell and prolactin responses were drawn from ICU patients who did not receive dopamine. A severity-of-disease score (Acute Physiology and Chronic Health Evaluation [APACHE II] score) was recorded for all patients.. Serum prolactin concentrations decreased > 90% (p < .001) within hours in all patients receiving dopamine infusions at study dose limit or above. The in vitro T-cell proliferative response to concanavalin A decreased (a transitory response) in patients receiving a dopamine infusion (p < .001). Dopamine infusions in medical ICU patients produced an immediate and profound reduction in serum prolactin concentrations in both males and females. An immediate transitory decrease in patient T-cell response to concanavalin A stimulation in vitro was seen in patients receiving dopamine.. The data suggest the possibility of altered endocrine and immune function as a corollary of therapeutic concentrations of dopamine in critically ill patients.

Topics: Concanavalin A; Critical Illness; Dopamine; Female; Humans; Leukocyte Count; Lymphocyte Activation; Male; Prolactin; Prospective Studies; Radioimmunoassay; Severity of Illness Index

Critical illness is associated with both immunosuppression and glutathione deficiency. We determined if in vivo depletion of glutathione would adversely affect immune status. Rats with normal glutathione levels and those with glutathione stores depleted by diethyl maleate underwent analysis of splenocyte function and mesenteric lymph node lymphocyte function. Lymphocytes of the spleen and mesenteric lymph nodes were tested for concanavalin A proliferative response and interleukin 2 production. Tumor necrosis factor and interleukin 6 secretion by splenic adherent cells was also measured. Glutathione-depleted animals had significantly decreased lymphocyte proliferation and decreased production of tumor necrosis factor and interleukin 6 but unaltered interleukin 2 production. These findings indicate that in vivo glutathione deficiency impairs macrophage and T-cell function. Because glutathione depletion may occur in sepsis, trauma, and shock, treatments that help maintain glutathione levels may enhance immunocompetence and thus improve the ability of patients to recover from critical illness.

Topics: Animals; Concanavalin A; Critical Illness; Disease Models, Animal; Evaluation Studies as Topic; Glutathione; Immune Tolerance; Immunity, Cellular; Interleukin-2; Interleukin-6; Lymph Nodes; Lymphocyte Activation; Macrophages; Rats; Rats, Wistar; Spleen; T-Lymphocytes; Tumor Necrosis Factor-alpha