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Potent chemotactic activity for neutrophils was detected in rat inflammatory exudate induced by a subcutaneous injection of lipopolysaccharide in a carboxymethyl-cellulose suspension. We purified and characterized chemoattractants from the exudate by the following procedures: carboxymethyl-Sephadex C-25 ion-exchange chromatography; G3000SW gel-filtration chromatography; preparative reverse-phase high-pressure liquid chromatography; rechromatography on reverse-phase HPLC. Two chemotactic factors were purified and their N-terminal amino acid sequences were determined. One factor was a protein in which the first 20 N-terminal amino acids were identical to those of rat cytokine-induced neutrophil chemoattractant (CINC), a counterpart of human gro/melanoma growth-stimulating activity (MGSA). The other factor was highly similar to mouse macrophage inflammatory protein 2 (MIP-2). Mouse MIP-2, a chemotactic factor for neutrophils, is a member of the interleukin-8 family; however the protein we purified had higher similarity to human gro/MGSA than to human interleukin-8. These results indicate that, in rats, chemotactic factors for neutrophils induced by lipopolysaccharide stimulation are not counterparts of interleukin-8, but are gro/CINC-related peptides.

The development of immune response in rats directed toward EL4 cells, after the injection of EL4 cells suspended in a saline/oil emulsion, was enhanced by the incorporation of Mycobacterium into the saline/oil emulsion; the incorporation of type II collagen into the saline-acetic acid/oil emulsion in concentrations ranging from 0.5-25 micrograms/ml had no apparent effect on the development of immune response. The incorporation of type II collagen into the saline-acetic acid/oil emulsion at higher concentrations (100 micrograms and 1.0 mg/ml) significantly suppressed both the humoral and the cell-mediated immune response. Pretreatment of rats with the maximal subarthritiogenic dose of complete Freund's adjuvant prevented the development of arthritis in response to a subsequent injection of an arthritogenic dose of the same adjuvant, but had no effect on the development of type II collagen-induced arthritis. These observations suggest that adjuvant arthritis and the type II collagen-induced arthritis are distinctly different diseases.

[(Cycloalkylmethyl)phenyl]acetic acid derivatives and related compounds were synthesized to test their antiinflammatory and analgesic activities. Some of the compounds in this series were found to have good activity in the carrageenan edema test. Among them, sodium 2-[4-[(2-oxocyclopentyl)methyl] phenyl]propionate dihydrate (15) and 2-[4-[(2-oxocyclohexylidene)methyl]phenyl]propionic acid (13b) showed potent analgesic and antiadjuvant arthritis activities with excellent antipyretic properties.