Nerve growth factor inhibits some acute experimental inflammations

Abstract

Nerve growth factor (NGF) displays an inhibitory effect on peritoneal dye leakage in mice and on some types of acute inflammation in rats, i.e. acetic acid peritonitis and paw oedema induced by carrageenin, serotonin and dextran. Activity was only present in a restricted dose range, either after subcutaneous (1-8 micrograms/kg) or subplantar (0.5-5 micrograms) injection, and was characterized by a rapid onset of response. In the carrageenin test, NGF administered s.c. was more potent than indomethacin (INDO) and betamethasone (BTM); in addition, while the activity of INDO and BTM was observed only 2-3 hr after carrageenin challenge, the response of NGF developed within 1 hr, suggesting that NGF inhibits the early phase of the oedema. NGF exhibited a different action than BTM and INDO also in serotonin and dextran paw oedema. NGF (0.008 mg/kg s.c.) inhibited the serotonin oedema as early as 15 min and reached its maximum at 1 hr, whereas BTM (0.8 mg/kg) required at least 3 hr to attain the same effect. Serotonin oedema was not inhibited by INDO (even at 16 mg/kg) up to 0.25-6 hr, proving that this model of inflammation is insensitive to the inhibitors of prostaglandin synthesis. When given subplantary, NGF reduced dextran oedema, whereas BTM and INDO were ineffective. Pretreatment with specific anti-NGF antibodies abolished all the above effects of NGF, but did not modify the anti-inflammatory activity of BTM and INDO. NGF was less effective in reducing the exudate volume on carrageenin pleurisy and did not prevent cell migration. Tested in vitro, NGF showed no direct scavenging effect on superoxide radicals. These findings suggest that NGF may be involved in some types of acute inflammation by reducing vascular permeability.