Ibuprofen restores cellular immunity and decreases susceptibility to sepsis following hemorrhage.
Although hemorrhage depresses splenocyte (SPL) functions and increases susceptibility to sepsis, it is not known whether increased tumor necrosis factor (TNF) or prostaglandin (PG) production are responsible for it. To study this, mice (C3H/HeN) were bled to a mean blood pressure of 35 mm Hg, maintained at that pressure for 60 min, resuscitated, and treated with ibuprofen (1.0 mg/kg body weight) or vehicle (saline). Hemorrhage reduced (P less than 0.05) SPL proliferation by 60%, SPL release of interleukin-2 (IL-2) by 47%, interferon-gamma (IFN-gamma) by 67%, TNF by 54%, and interleukin-6 (IL-6) by 46% compared to sham. In addition, splenic macrophage (sM phi) release of interleukin-1 (IL-1) and TNF was decreased by 58 and 67% (P less than 0.05), respectively. However, ibuprofen treatment increased (P less than 0.05) SPL proliferation, lymphokine (IL-2, IFN-gamma, and IL-6) synthesis, and IL-1 release by sM phi compared to hemorrhage alone. Furthermore, ibuprofen enhanced the release of TNF by SPL (+175%, P less than 0.05) and sM phi (+68%) compared to the vehicle group. Ibuprofen also decreased (P = 0.011) the susceptibility to sepsis following hemorrhage. These results indicate that PGs are involved in hemorrhage-induced suppression of cellular immunity and in the increased mortality of such animals following a septic challenge.
Ertel
W
W
Department of Surgery, Michigan State University, East Lansing 48824.
Morrison
M H
MH
Meldrum
D R
DR
Ayala
A
A
Chaudry
I H
IH
D000818:Animals; D001794:Blood Pressure; D002478:Cells, Cultured; D003208:Concanavalin A; D016207:Cytokines / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004198:Disease Susceptibility; D006470:Hemorrhage / Q000276:immunology / Q000503:physiopathology*; D007052:Ibuprofen / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects* / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018805:Sepsis / Q000503:physiopathology / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D007052:Ibuprofen