Diminished bacterial clearance is associated with decreased IL-12 and interferon-gamma production but a sustained proinflammatory response in a murine model of postseptic immunosuppression.

Murphey ED, Lin CY, McGuire RW, Toliver-Kinsky T, Herndon DN, Sherwood ER
Shock. 2004 21 (5): 415-25

PMID: 15087817 · DOI:10.1097/00024382-200405000-00004

After a major illness or injury, immune status in critically ill patients may fluctuate between a marked proinflammatory response and an immunosuppressed state. Postinflammatory immunosuppression can result in increased susceptibility to infection. Alterations of cytokine production, such as suppression of IFNgamma and elevation of the anti-inflammatory cytokine IL-10, are believed to contribute to postinflammatory immunosuppression. We examined antimicrobial immunity in mice that had previously been subjected to a sublethal cecal ligation and puncture (CLP) as a model of major injury. Mice were challenged with Pseudomonas aeruginosa (5 x 10(7) CFU i.v.) on day 5 after CLP or sham surgery. Bacterial clearance in mice after CLP was impaired and associated with decreased production of IFNgamma and increased production of IL-10 in the early response to the Pseudomonas challenge. Pseudomonas-induced production of the IFNgamma-inducing factor IL-12 was also decreased in post-CLP mice. However, splenocytes from post-CLP mice remained responsive to exogenous stimulation with the IFNgamma-inducing cytokines IL-12, IL-15, and IL-18 as well as T-cell receptor activation. Furthermore, production of the proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were as high, or higher, in the post-CLP group compared with sham mice after P. aeruginosa challenge. Blockade of IL-10 did not reverse IL-12 and IFNgamma suppression in splenocytes from post-CLP mice. These studies show that suppressed bacterial clearance in post-CLP mice is associated with decreased production of IFNgamma and IL-12 and with increased production of IL-10 and proinflammatory cytokines.

MeSH Terms (27)

Animals Cecum Cytokines Disease Models, Animal Enzyme-Linked Immunosorbent Assay Flow Cytometry Humans Immune Tolerance Immunosuppression Immunosuppressive Agents Inflammation Interferon-gamma Interleukin-1 Interleukin-6 Interleukin-10 Interleukin-12 Interleukin-15 Interleukin-18 Male Mice Mice, Inbred C57BL Pseudomonas aeruginosa Ribonucleases Sepsis Spleen Time Factors Tumor Necrosis Factor-alpha

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