Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandin and collagenase, and thymocyte proliferation is augmented in response to one protein.

Homogeneous catabolin from pig leucocytes induced proteoglycan breakdown, but not collagen breakdown, in explants of articular cartilage. It augmented lectin-induced proliferation of mouse thymocytes, stimulated production of prostaglandin E2 and collagenase by fibroblasts and chondrocytes, and increased Ca2+ release from mouse calvarial explants, all at concentrations down to 50 pM. In view of these effects it was concluded that pig catabolin is a form of interleukin 1.

The cartilage-resorbing protein catabolin is made by synovial fibroblasts and its production is increased by phorbol myristate acetate.

Pig synovial fibroblasts were shown to produce a protein that caused live cartilage to resorb its proteoglycan matrix in vitro. Fibroblasts were obtained either from synovial tissue digest or by allowing them to grow out of explants. The population derived from the digests was homogeneous and free of macrophage-like cells after two passages, but was still producing the cartilage-resorbing protein after seven passages. The active protein was found to have Mr 20,000 on gell filtration, and pI 4.8 on isoelectric focussing in polyacrylamide gel. It was indistinguishable from a protein with the same activity from pig mononuclear leucocytes, which has been called catabolin. Production of the protein was increased if the synovial fibroblasts were cultured with the tumour promoter phorbol 12-myristate 13-acetate. Fibroblasts from other sources (joint capsule and peritoneum) also apparently made the protein. The possibility that catabolin is the same as interleukin-1 is discussed: if they are, then the results suggest that fibroblasts can make an interleukin-1-life protein.

Characterization of proteins from human synovium and mononuclear leucocytes that induce resorption of cartilage proteoglycan in vitro.

Both human synovial tissue in culture and lectin-stimulated mononuclear leucocytes produced a protein that induced proteoglycan resorption in explants of bovine nasal cartilage and human articular cartilage. On gel filtration the protein had Mr 16000-20000 and on isoelectric focusing its pI was 5.2-5.3. The protein corresponded to catabolin, which has previously been identified as a product of cultured porcine synovial tissue and mononuclear leucocytes. The action of partially purified human catabolin was not inhibited by cortisol, although the activity of the leucocyte supernatants from which it had been isolated was inhibited. For this reason it is not possible to be sure that the active factor detected in the bioassay of the crude leucocyte culture supernatants is in fact catabolin.

Effects of antirheumatoid drugs on the production and action of porcine catabolin.

We report the effects of some common antirheumatic drugs on the production of catabolin from synovium and on its action on cartilage. A method is described to generate reproducible amounts of catabolin from synovial mince. Aspirin, Clozic (ICI 55,897), and gold were without effect on the catabolin system. Penicillamine at high doses enhanced the action of catabolin, while chloroquine inhibited catabolin's effect on cartilage. Prednisolone inhibited the production of catabolin without affecting its action. This inhibition was produced by very low doses of prednisolone (25 ng/ml) and was dose-dependent.

Effects of obstruction of the flow of seminiferous tubule fluid on the germinal epithelium in the rat.

Blocking the lumen of a single seminiferous tubule by introducing a plug of non-toxic latex produced a lesion in that tubule, but not in immediately adjacent tubules. The lesion extended for up to 50 mm from the end of the latex. Nearest to the block the tubule was completely aspermatogenic; further along the tubule, the lesion was less severe, involving disorganization and reduction in germ cell numbers, with the cells showing vacuolation, pycnosis and karyolysis. Binucleate and giant cells were common, and cells were often exfoliated into the lumen. The lesion tended to increase in length with longer times after introduction of the plug, but there appeared to be no preferential involvement of the shorter segment of the tubule between the block and the rete. The transition from damaged to healthy tubule was abrupt.