Studies on Inflammation

Abstract

Various types of inflammatory exudates have been obtained either by the introduction into normal tissues of a chemical irritant, or by a burn, or by bacteria in either dogs or rabbits. A study has also been made on an exudate of human origin. These exudates have all been found to contain a factor which induces prompt increase in the permeability of normal skin capillaries, demonstrable by the almost immediate accumulation from the circulation of trypan blue into areas of skin injected with the cell-free exudate. The active factor may be carried down with the precipitate resulting from the interaction of the exudate with either saturated ammonium sulfate or 20 per cent sodium sulfate. The active factor passes through a dialyzing membrane. It can be recovered from the dialysate as a protein-free crystalline material. The active factor manifests no property in common with histamine or presumably with the hypothetical H substance assumed to be closed related to histamine. This is indicated by the following considerations: (a) difference between the tissue staining pattern of the exudate or of its active fraction and that of histamine; (b) opposite effects by histamine and the active factor found in exudates on the tonicity of the isolated strip of guinea pig intestine. The observations presented in this report do not substantiate Lewis' hypothesis of histamine or of its closely related H substance as the primary cause of increased capillary permeability in inflammation. The present studies are being continued in an endeavor to free of its impurities and to identify the active crystalline-like material isolated from an inflammatory exudate. The details of this investigation will form the subject of a separate future communication.

Studies on inflammation. XIV. Isolation of the factor concerned with increased capillary permeability in injury

“…for several days, favored the separation of a brownish, flocculating mass. This substance, taken up in distilled water and injected intracutaneously in a rabbit, increased the permeability of skin capillaries, as indicated by the usual test (2).…”

“…had demonstrated t h a t the permeability factor recovered from exudates, unlike histamine, fails to induce a contraction of the isolated intestine of a guinea pig (2). Other evidences failing to support the identity of the permeability factor and of histamine were described at the time and will therefore not be taken up again (2,4).…”

“…of turpentine (2). The exudate resulting from the intraperitoneal injection of an aleuronat-starch mixture in a rabbit was likewise studied.…”

“…Diffusibility.--In an earlier communication, it was pointed out that the active permeability factor of exudates readily diffuses through a cellophane membrane (2). As pointed out above, the supernatant acetone fraction containing the active substance may be dialyzed for several hours against distilled water (Table I).…”

“…carried down with the precipitate that forms by the interaction of the exudate with saturated ammonium sulfate (2). Likewise, the addition of the relatively pure fraction of the material to a saturated solution of ammonium sulfate is soon followed by the appearance of a small but definite cloudy suspension.…”