CYTOKINE EXPRESSION IN EXPERIMENTAL GRAM-NEGATIVE INFECTION

To examine the early pattern of cytokine gene expression in gram-negat ive sepsis, we have monitored mRNA levels of IL-1, IL-6 and TNFalpha i n the spleens of mice undergoing lethal (''nonhealer mice'') or sublet hal (''healer mice'') acute infection with live Pseudomonas aeruginosa cells. Spleens were harvested at 0.5, 2, 4, 8, 24, and 48 hr after in travenous inoculation of different challenge doses of the bacterium, a nd PCR-assisted mRNA amplification was performed on matched samples us ing cytokine-specific primers. The timing and pattern of message detec tion did not differ qualitatively by IL-1, IL-6 or TNFalpha mRNA expre ssion in early spleen cells from healer vs nonhealer mice. However, in the lethally challenged mice, high levels of specific messages were d etected throughout the course of infection. In the healer mice, a prog ressive reduction in cytokine mRNA expression was found to concur with recovery from the critical stage of the disease. These data support t he notion that the severity of gram-negative infection might correlate with the pattern of cytokine cascade elicited in the host (Fund. Clin . Immunol. 2: 97-99, 1994).