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OM-89 is a bacterial extract from escherichia coli, proposed as an immunomodulating drug for the treatment of rheumatoid arthritis (RA). Since immunological mechanisms may play a role in its action, the immunological effects of OM-89 were evaluated in vitro on peripheral blood mononuclear cells (PBMC) derived from healthy subjects and RA patients. Results indicated that in the absence of OM-89, production of the monokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) is increased, while that of the lymphokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma is decreased by phytohemagglutinin (PHA)-stimulated PBMC from RA patients as compared with PBMC from healthy subjects. In the presence of PHA, OM-89 enhanced the production of IL-1 beta, TNF-alpha, IL-2, and IFN-gamma. IL-1 beta and IL-2 curves obtained using increasing amounts of OM-89 did not differ depending on the source of PBMC. By contrast, in the presence of increasing amounts of OM-89, TNF-alpha secretion significantly higher and IFN-gamma secretion significantly lower with PBMC from RA patients compared to PBMC from healthy subjects. These data indicate that OM-89 acts on monocytes and T cells directly and/or indirectly and suggest a possible clinical activity by OM-89 in RA relative to its immunological properties.

Using radio-immunoassay methods, the production of tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) released by peripheral blood mononuclear cells (PBMC), maintained in culture and stimulated by phytohemagglutinin (PHA), was measured in normal subjects and patients with active or inactive rheumatoid arthritis (RA). Results indicated a dissociation between mitogenic response and secretion of mediators by PBMC under the influence of PHA in both normal controls and in patients with rheumatoid arthritis (RA). While [3H]thymidine incorporation was characterized by a rather bell-shaped curve with increasing concentrations of PHA, IL-2 and TNF-alpha displayed a linear dose-dependent increase. [3H]thymidine uptake by PBMC was in the same range in normal subjects as in patients with active and inactive RA, although cytokine secretion differed. The PBMC of patients with active RA produced less TNF-alpha, IL-2, and IFN-gamma than did those of the controls. In cases of inactive RA, the secretory response varied from subject to subject; mean values did not differ from those of normal subjects, except for those of IL-2 (p less than 0.01). The significance and the clinical relevance of these findings are discussed.