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Histamine type-2 receptor antagonist immune modulation II. Cimetidine and ranitidine increase interleukin-2 production

  • Robert R.M. Gifford
    Correspondence
    Reprint requests: Robert R.M. Gifford, M.D., Department of Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033.
    Affiliations
    From the Department of Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pa., USA
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  • Anna F. Tilberg
    Affiliations
    From the Department of Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pa., USA
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      Abstract

      The effect of cimetidine and ranitidine (histamine type-2 receptor antagonists) on the production of interleukin-2 (IL-2) by mitogen-activated, normal murine spleen cells was studied in vitro. Cimetidine (10−4 mol/L to 10−6 mol/L) increased IL-2 production to a maximal 8.8 ± 1.6 U (IL-2 activity), as compared with media controls of 1 U. Ranitidine (10−4 mol/L to 10−6 mol/L) also increased IL-2 production to a maximal 5.6 ± 1.2 U, as compared with media controls of 1 U. The increases for both drugs were statistically significant (p at least < 0.03 for all doses tested). These data suggest that our previously demonstrated immunofacilitation of proliferative and cytotoxic lymphocyte responses by cimetidine was probably mediated by the presence of increased IL-2. These data further suggest that histamine type-2 receptor antagonists may have immunorestorative potential in clinical immunotherapy of IL-2 deficient states.
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