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In this work we have studied the acute phase protein response and degranulation of polymorphonuclear leukocytes in vivo in the rat after a slow interleukin-1beta stimulation. A total dose of 1 mug, 2 mug, 4 mug and 0 mug (controls with only vehicle) of interleukin-1beta was released from osmotic minipumps over a period of 7 days. The pumps were implanted subcutaneously. A cystic formation was formed around the pumps that contained interleukin-1beta whereas no tissue reaction was seen around pumps containing only vehicle. Besides flbroblasts the cyst wall contained numerous polymorphonuclear leukocytes which were positively stained for cathespin G. alpha(2)-macroglobulin, alpha(1)-inhtbitor-3, alpha(1)-proteinase inhibitor, albumin and C3 were measured by electroimmunoassay and all showed plasma concentration patterns that were dose-dependent to the amount of interleuktn-1beta released. Fibrinogen in plasma was elevated in the control group but showed decreased plasma values with higher doses of interleukin-1beta released. All animals showed increased plasma levels of cathespin G but the lowest levels for cathespin G were seen for the highest interleukin-1beta dose released. It was clearly seen that a slow continuous release of interleukin-1beta in vivo caused an inflammatory reaction. Plasma levels for the proteins analysed all showed a similar pattern, namely an initial increase or decrease of plasma concentration followed by a tendency to normalization of plasma values. It was concluded that a long-term interleukin-1beta release could not sustain the acute phase protein response elicited by the initial interleukin-1beta release.

Acute Phase Protein Response and Polymorphonuclear Leukocyte Cathepsin G Release After Slow Interleukin-1 Stimulation in the Rat