Lymphocyte-derived cytokines augment macrophage tumor necrosis factor-alpha and interleukin-6 secretion during experimental gram-negative bacterial sepsis.

ABSTRACT

Although lymphocyte-derived cytokines are known to augment macrophage cytokine production in vitro, their effect on macrophage tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion during gram-negative bacterial sepsis has not been characterized. The purpose of this study was to examine the effect of lymphocyte-derived cytokines on macrophage TNF-alpha and IL-6 secretion during gram-negative bacterial peritonitis. To examine this problem, uninfected and infected mice were studied. Mice were infected with Escherichia coli O111B4 and two subgroups were examined consisting of those pretreated iv 1 hr prior to bacterial challenge with either (1) saline or (2) anti-E. coli O111B4 LPS mAb 2A3, the latter administered to abrogate the effects of LPS in vivo. Thus, three groups of mice were studied in relation to pretreatment and infectious challenges (1) saline/saline (control); (2) saline/E. coli (saline); and (3) mAb 2A3/E. coli (mAb 2A3). Nonadherent splenocytes (> 95% lymphocytes by histologic staining criteria) harvested 16 hr later from mice in each group were incubated in culture ex vivo for 3 hr to obtain supernatants containing lymphocyte-derived cytokines. These supernatants containing lymphocyte-derived cytokines then were incubated in vitro with naive splenic macrophages with or without E. coli O111B4 LPS. Macrophage TNF-alpha and IL-6 levels were determined using L929 and B9 bioassays.(ABSTRACT TRUNCATED AT 250 WORDS)