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Nitric oxide (NO) has been recently identified as a potent mediator of tumoricidal activity of activated macrophages. Macrophages can be activated for tumor cell killing by microbial products, including lipopolysaccharide (LPS) and various cytokines. Here we report that in contrast to mouse macrophages, human peripheral blood monocytes stimulated with cytokines or LPS failed to release NO. Also priming of monocytes with interferon-gamma followed by activation with cytokines or LPS did not cause NO secretion. However, monocytes responded with NO production to stimulation with some human cancer cells but not with untransformed cells. NO production by monocytes was inhibited by NG-monomethyl-L-arginine, specific inhibitor of NO synthase and emetine, an irreversible blocker of protein synthesis. This may imply that human monocytes are unique in their restricted capacity to produce NO following interaction with some tumor cells, but not with other stimulators, and in this respect they may be able to distinguish between malignant and normal cells.

The lymph node cells of CBA (H-2k), but not BALB/c (H-2d) mice, release interferon (IFN)-gamma into the supernatant when immunized with picryl chloride epicutaneously and then exposed to antigen (haptenized cells) in vitro 4 days later. The failure in IFN-gamma production maps to the major histocompatibility complex (MHC; H-2d) in the congenic BALB/c, BALB/k and BALB/b mice. The evidence that this is an MHC regulation of the class of response to a range of antigens and not a classical Ir gene effect is (a) the difference is seen with several antigens including picryl chloride, "oxazolone" and purified protein derivative of tuberculin and (b) BALB/c mice, which fail to produce IFN-gamma, show excellent contact sensitivity to picryl chloride. It was also found that the crosses between responder and nonresponder strains (CBA x BALB/c)F1 respond to antigen on responder cell but not on nonresponder cells. This influence of MHC on the class of the immune response is a possible basis for some of the associations of MHC with disease.