Macrophages can be activated to produce reactive oxygen intermediates, such as superoxide anion (O2-), which are responsible for intracellular killing of pathogenic microbes. Treatment with either native or recombinant somatotropin augmented the production of O2- by both peripheral blood-derived and alveolar macrophages stimulated with opsonized zymosan in vitro. This effect was abolished by prior treatment with an antibody specific for somatotropin. When either native or recombinant porcine somatotropin or native rat somatotropin was administered to hypophysectomized rats in vivo, activation of peritoneal macrophages, as measured by release of O2- in response to opsonized zymosan, was equivalent to that of macrophages from rats primed with the macrophage-activating factor interferon-gamma. Priming of macrophages in vivo was observed at physiologically relevant doses of somatotropin that caused a 10 to 40 percent increase in growth rate. Priming of mononuclear phagocytes for augmented production of reactive oxygen metabolites is a newly defined property of somatotropin.

Evidence has been obtained to indicate that cyclodiene-type insecticides, e.g., heptachlor epoxide and gamma-BHC, mimic the action of picrotoxinin. These insecticides inhibit the GABA (gamma-aminobutyric acid)-stimulated chloride uptake in the coxal muscle of the American cockroach, and directly compete against [3H]a-dihydropicrotoxinin for binding in the rat brain synaptosomes. Moreover, several cyclodiene-resistant insect strains are also resistant to picrotoxinin. This cross-resistance is specific to picrotoxinin and does not extend to other neuroexcitants. These insecticides, like picrotoxinin, cause central nerve excitation by stimulating transmitter release. Similarity in molecular structures also has been pointed out. These results indicate that some of the nerve excitation symptoms that insecticides cause are likely due to their interaction with picrotoxinin receptor.

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Purified and recombinant forms of growth hormone (GH) as well as of recombinant rat gamma interferon (IFN-y) enhance the survival of rats deprived of endogenous pituitary GH secretion by hypophysectomy (HX rats) and infected with virulent SalmoneUla typhimurium. Macrophages obtained from rats with intact pituitaries (pituitary-intact rats) or HX rats that were treated in vivo with either GH or the closely related hormone prolactin released elevated (P < 0.05) levels of superoxide anion (02-) after in vitro opsonizedzymosan stimulation compared with those from placebo-treated animals. These levels of 02 release were similar in magnitude to those of macrophages from rats treated in vivo with IFN-y. In time course in vivo macrophage activation studies, both IFN-'y and GH significantly increased°2secretion within 24 h, with maximal secretion occurring at day 3. Macrophages obtained from pituitary-intact and HX rats injected in vivo with GH also released elevated (P < 0.05) levels of hydrogen peroxide (H202) and displayed enhanced (P < 0.01) phagocytic activity toward opsonized Listeria monocytogenes in vitro. The mechanism of action of GH in vivo is likely to be a direct one because resident peritoneal macrophages from rats could be primed in vitro for enhanced secretion of 02 following triggering of these cells with opsonized zymosan. These data show that in vivo administration of two closely related pituitary hormones, GH and prolactin, can effectively prime macrophages, which is consistent with the hypothesis that GH mediates resistance to S. typhimurium by a direct stimulatory action on macrophages.