Immune responses and immunoregulation in relation to human schistosomiasis in Egypt. II. Cimetidine reversal of histamine-mediated suppression of antigen-induced blastogenesis.
The effect of histamine on cell-mediated immune responses of chronic schistosomiasis patients was tested by peripheral blood mononuclear cell (PBMN) reactions to phytohemagglutinin-P (PHA) and soluble schistosomal antigenic preparations derived from eggs (SEA) or adult worms (SWAP). PBMN responses to PHA were suppressed by exogenous histamine (10(-5)M), and the addition of cimetidine (CIM) (10(-4)M), an H2-receptor antagonist, reversed this suppressive effect. Histamine primarily suppressed PBMN responses to suboptimal and optimal PHA concentrations. Exogenous histamine (10(-5)M) also suppressed PBMN responses of 27 schistosomiasis patients to SEA and SWAP, respectively. The addition of CIM (10(-4)M) to suppressed cultures reversed the effect of exogenous histamine. Most importantly, the addition of CIM to schistosomal antigen-induced cultures, without exogenous histamine, significantly increased patients' PBMN responses to SEA and SWAP. The mean optimal increase in SEA responses of 19 patients was 390%. With SWAP-induced responses of 21 patients this increase was 165%. The use of 10(-4)M diphenhydramine (DPH), an H1-receptor antagonist, resulted in general suppression of both PHA-induced and schistosomal antigen-induced PBMN responses. Lower concentrations of DPH lead to variable responses but did not result in consistent abrogation of the histamine-induced suppression. These data imply that an histamine-induced, H2-receptor-mediated suppressor circuit often helps modulate antigen-specific responsiveness of PBMN from patients with chronic schistosomiasis.
D000328:Adult; D000941:Antigens / Q000276:immunology; D002927:Cimetidine / Q000494:pharmacology*; D004534:Egypt; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007814:Larva / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010063:Ovum / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012548:Schistosoma haematobium / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology; D012552:Schistosomiasis / Q000276:immunology*
D000941:Antigens; D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D002927:Cimetidine; D006632:Histamine