STUDIES ON INFLAMMATION : XII. MECHANISM OF INCREASED CAPILLARY PERMEABILITY. A CRITIQUE OF THE HISTAMINE HYPOTHESIS

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.