Immunomodulation with Synthetic Molecules: Mechanisms of Actions and Effects on Macrophages.
Annual rept. no. 1, 1 Nov 82-31 Oct 83,
INSTITUTE FOR MEDICAL RESEARCH SAN JOSE CA
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Immunoenhancing drugs were studied both for their general effects on host immunity and their effects on immune interactions with microbial infections. These studies focused preferentially on defined single molecules with immunomodulating properties, and on fungi as the microbes of interest. The prototype immunomodulator studied was muramly dipeptide MDP. We showed that MDP in vivo enhanced cellurity and mitogen responses in some lymphoid compartments lymph nodes and depressed responses in other spleen. The optimum dose and interval for effect were defined, and subpopulations of the compartments were fractionated which were responsible for differences observed with different mitogens including suppressor cells. We also showed that polymorphonuclear leukocytes PMN can be activated as a byproduct of an immunological reaction, and in that state have enhanced fungicidal activity and can kill some fungi which normal PMN cannot. Activation could be reproduced with lymphokines. We showed that CP46665, a lipoidal amine, in vivo enhances fungicidal activity of PMN and alveolar macrophages AM, but had no in vitro effect. However, interferon, produced by gene cloning recombinant DNA techniques, had an adverse effect on PMN or AM antifungal activity.
- Medicine and Medical Research