[Macrophage colony-stimulating factor in patients with rheumatoid arthritis].

Macrophage colony-stimulating factor (M-CSF) is a cytokine involved in the development and proliferation of the monocyte/macrophage lineage cells. M-CSF has also been reported to participate in the induction of osteoclasts, and may be important in the destruction of bone and cartilage and the periarticular osteoporotic changes seen in patients with rheumatoid arthritis (RA). We developed a new ELISA technique to measure M-CSF levels in synovial fluid with high sensitivity and reproducibility. The mean M-CSF level in the synovial fluid of patients with RA was 1.38 +/- 0.56 ng/ml, and that of patients with osteoarthritis (OA) was 0.67 +/- 0.13 ng/ml. In contrast, serum levels of M-CSF in patients with RA and in normal controls were 1.32 +/- 0.50 ng/ml and 0.90 +/- 0.09 ng/ml, respectively. These differences were both statistically significant. Since serum M-CSF levels correlate with inflammatory signs obtained from examination of blood, they indicate the general condition of patients with RA. Synovial fluid M-CSF levels increase even in the early phase of RA and remain high despite drug therapy, which suggests that they reflect the condition of affected joints including joint spaces and inflamed synovia more directly than do the levels of serum M-CSF. Measurement of the M-CSF level in the synovial fluid may be useful in the diagnosis, clinical evaluation, and assessment of the effects of treatment in patients with RA.

Characterization of macrophage colony-stimulating factor in body fluids by immunoblot analysis.

We characterized the molecular species of human macrophage colony-stimulating factor (hM-CSF) found in serum and urine, using immunoblot analysis after partial purification on an antibody-bound affinity column. Although antibodies were prepared using the recombinant product of the large form of hM-CSF with a molecular weight (MW) of 85 Kd as the antigen, this immunoblot system was also capable of detecting the small form of hM-CSF with a MW of 40 to 60 Kd. A single band with a MW of 43 Kd, which reacted with anti-recombinant hM-CSF IgG but not with control IgG, was found when serum and urine from normal adults underwent electrophoresis on reduced sodium dodecyl sulfate-polyacrylamide gel and subsequent immunoblotting. This band represented a subunit of the large form of hM-CSF, because the large form of hM-CSF is a homodimer of a subunit with a MW of 43 Kd and the small form of hM-CSF is a homodimer of a subunit with a MW of 20 to 30 Kd. Analysis of serum and urine from leukemic patients and pregnant women, who had higher serum levels of hM-CSF than normal adults, showed only a single band with a MW of 43 Kd as a hM-CSF-specific molecule. These results suggest that the large form of hM-CSF is the major species in human body fluids.