ALTERATIONS IN RAT PERIPHERAL-BLOOD NEUTROPHIL FUNCTION AS A CONSEQUENCE OF COLITIS

Altered peripheral neutrophil function is a feature of IBD that may co ntribute to the chronicity and extragastrointestinal manifestations of this disease, but clinical evidence for such alterations is confounde d by variations in patient characteristics, disease onset, and use of therapeutics that can influence neutrophil function. The use of a rat model of colitis has permitted us to characterize, in a controlled man ner, the causal relationship between colitis and altered peripheral ne utrophil function. At various times after induction of colitis with tr initrobenzene sulfonic acid (TNBS), peripheral neutrophils were isolat ed and assays of phagocytosis, chemotaxis, leukotriene B-4 (LTB(4)) sy nthesis, and superoxide production were performed using a variety of s timuli. Circulating neutrophil numbers increased about fourfold within 12 hr of TNBS administration and returned to normal levels over the f ollowing two weeks. LTB(4) synthesis in response to calcium ionophore decreased at 12 hr after induction of colitis, then returned to contro l levels. The chemotactic responses of peripheral neutrophils to LTB(4 ) and FMLP in vitro and to LTB(4) and IL-8 in vivo were profoundly sup pressed through the two-week study period. Phagocytosis of nitroblue t etrazolium was significantly enhanced (ca. threefold) at 12 hr after i nduction of colitis and remained elevated throughout the study period. Superoxide production was also significantly elevated in the early ph ase of colitis (by ca. fourfold), but was not different from control l evels at seven and 14 days. These results demonstrate that colonic inf lammation profoundly influences peripheral blood neutrophil function, although the direction and magnitude of the alteration varied among th e various functions assessed. The prolonged depression of chemotactic activity may represent a physiological reaction to limit the inflammat ory response.