Blockade of prostaglandin production increases cachectin synthesis and prevents depression of macrophage functions after hemorrhagic shock.
Although hemorrhage severely depresses macrophage functions, it is not known whether the increased TNF-alpha or PGE2 production is responsible for it. To study this C3H/HeN mice were bled to mean blood pressure of 35 mmHg for 60 minutes, resuscitated, and treated with either ibuprofen (1.0 mg/kg body weight) or vehicle (saline). Hemorrhage increased plasma prostaglandin E2 (PGE2) levels by 151.7% +/- 40.0% (p less than 0.05) and significantly decreased peritoneal macrophage (pM phi) antigen presentation (AP) by 60.5% +/- 7.3%, Ia expression by 52.3% +/- 7.6%, and interleukin-1 (IL-1) synthesis by 60.5% +/- 12.3% compared to shams. However ibuprofen treatment reduced PGE2 plasma levels by 61.3% +/- 12.1% and significantly increased AP (+237.0% +/- 95.3%), Ia expression (+72.8% +/- 27.5%), IL-1 synthesis (+235.7% +/- 134.7%), and cachectin synthesis (+485.8% +/- 209.0%) compared to vehicle-treated animals. These results indicate that prostaglandins but not cachectin are involved in the suppression of pM phi functions following hemorrhage because blockade of prostaglandin synthesis improved depressed macrophage functions despite enhanced cachectin synthesis.
Ertel
W
W
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Morrison
M H
MH
Ayala
A
A
Perrin
M M
MM
Chaudry
I H
IH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000097:blood* / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007052:Ibuprofen / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012771:Shock, Hemorrhagic / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007052:Ibuprofen