CYTOKINE REGULATION OF THE ACUTE-PHASE PROTEIN-LEVELS IN MULTIPLE-MYELOMA

Background Interleukin (IL) 6 has an important role in the regulation of acute-phase proteins (APPs) during an acute-phase response. We stud ied IL-6 and other cytokines to determine if they regulate serum APP l evels in the same way under the condition of the aberrant, longlasting 'acute-phase response' that occurs in patients with chronic inflammat ion and cancer. Methods Serum levels of nine positive APPs [CRP, SAA, C1-INH, Bf, C5, C8, C9, alpha(1)-acidic glycoprotein (AGP) and haptogl obin] and two negative APPs [transferrin and alpha(2)-HS glycoprotein (AHSG)] were measured using immunochemical methods in 59 multiple myel oma patients and in 72 healthy control subjects. Serum IL-6 and tumour necrosis factor (TNF) alpha levels were determined by bioassays. Resu lts IL-6 was negatively correlated with five out of nine (C1-INH, C8, C9, AGP and haptoglobin) positive APPs but positively correlated with C-reactive protein (CRP). When patients with high and low IL-6 serum c oncentration were compared, CRP levels were higher, AGP and haptoglobi n levels were lower in the high- than in the low-L-6 group, whereas no significant difference between the two groups was found in levels of the other positive and negative APPs. TNF-alpha levels were negatively correlated with transferrin and AHSG levels. No difference in the lev els of positive APPs was observed between patients with low and high T NF-alpha serum concentration. By contrast, levels of both transferrin and AHSG were significantly lower in the high- than in the low-TNF-alp ha group. Conclusions These findings indicate that, except for regulat ion of the negative APPs by TNF-alpha, the mechanism of APP regulation is different under the conditions of the short-term and the chronic, long-lasting 'acute-phase reaction'.