Complement was studied in 20 untreated cases of Crohn's disease and in 20 healthy volunteers by an in vitro activation of the cascade reaction. Total haemolytic complement was normal in all patients. In contrast, activation of the alternative pathway lead to a decreased release of C5a related chemo-attractant activity together with a subnormal utilisation of the main complement component C3. This abnormality of complement function was not related to the activity of the disease, site of involvement or to disease duration. The results suggest that an inadequate stimulation of important neutrophil functions may result when bacterial lipopolysaccharides and other macromolecules activating the alternative pathway penetrate the gut mucosa. A delayed clearance from the tissue of such foreign material could be a further pathogenic factor in Crohn's disease leading to granulomatous inflammation by a foreign body reaction.
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