Lymphocyte activating factor (LAF) and the acute-phase response in adjuvant arthritic rats

The purpose of the study was to determine the temporal relationship between lymphocyte activating factor (LAF) activity and the acute-phase response, as measured by plasma fibronectin (Fn), C-reactive protein (CRP), and albumin levels in adjuvant arthritic rats. LAF activity as measured in the thymocyte costimulator assay, and plasma Fn, CRP, and albumin levels were measured during the acute (Day 3), intermediate (Day 10), and systemic (Day 17) phases of arthritic disease. On Day 3, supernatants from whole spleen cells of adjuvant-injected rats did not exhibit abnormal LAF activity. By Day 10, LAF activity in splenic supernatants from arthritics was significantly (P less than or equal to 0.05) higher than normal, although the increase was no greater than 60%. On Day 17 the LAF activity from arthritic rats had increased an average 300% compared to normals. In contrast to the time course of IL-1 activity, Fn and CRP levels in the arthritic rat were significantly higher than normal at all three time points, although there was a transient fall in Fn and CRP concentrations on Day 10. Plasma albumin levels in arthritic rats were subnormal (P less than or equal to 0.01) on Days 3, 10, and 17, although the concentration of plasma albumin on Day 10 was significantly higher than that measured on Day 3. The acute, intermediate, and systemic phases of adjuvant arthritic paw inflammation paralleled the abnormal profile of Fn, CRP, and albumin concentrations over time. However, LAF activity from arthritic rat spleen cells increased gradually and more closely coincided with the systemic appearance of the disease. Since the appearance of abnormal plasma protein levels in arthritic rats preceded the appearance of increased splenic LAF activity, it appears that there is no causal relationship between enhanced splenic LAF activity and early alteration of plasma Fn, CRP, and albumin levels.