Activation of Human Monocytes and Alveolar Macrophages by a Synthetic Peptide of C-Reactive Protein

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Abstract
We have previously shown that native human C-reactive protein (CRP) produces antitumor effects in experimental animals, and that these effects are mediated primarily through macrophages. More recently, we have observed that RS-83277, a synthetic peptide derived from CRP, appears to mimic the antitumor effects of native CRP. The purpose of this study was to determine the effects of RS-83277 on normal human monocyte and alveolar macrophage tumoricidal activity, and cytokine secretion. At optimal doses of 250-500 micrograms/ml, RS-83277 significantly enhanced tumoricidal activity of both monocytes and macrophages. RS-83287, a CRP peptide derived from a different site, had no effect at these doses. Specificity of RS-83277 for monocyte/macrophage-mediated cytotoxic activity was demonstrated by the failure of RS-83277 to enhance either natural killer (NK) or lymphokine-activated killer (LAK) cell-mediated activity. RS-83277 also augmented secretion of interleukin-1-beta (IL-1 beta) and interleukin-6 (IL-6) by monocytes. These data suggest a role for synthetic CRP peptide, RS-83277, as a novel biological response modifier in cancer therapy.

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