Interleukin-1 alpha (IL-1 alpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) as potential inducers of supravital chemotaxis

The phenomenon of artificially induced local leucocyte reactions during the supravital period could be of practical importance, but has not yet been comprehensively investigated. For a more detailed evaluation, experiments with the chemotactic agents interleukin-1 alpha (IL-1 alpha) and N-formyl-methionyl-leucyl-phenylaline (FMLP) were performed by subcutaneous injection into various anatomical regions (back, abdomen, limbs) of NMRI-mice (National Medical Research Institute) and pigs 0-5 min after circulatory arrest. Phosphate buffered saline (PBS) without effective components was administered to equivalent areas of the animals as a control. Tissue specimens were collected at 6 h postmortem (mice) and 12-14 h postmortem (pigs), cut into serial sections, stained with H&E and examined under the microscope. A leucocyte reaction did not develop in pigs (n = 10, 30 tissue samples) following injection of FMLP, however, dermal, subcutaneous and perivascular infiltration of leucocytes (in particular mononuclear cells and a few granulocytes) was found in 3 out of 30 tissue specimens in murine experiments. In addition intravascular cell accumulations were detected in 2 out 30 samples. The injection of IL-1 alpha to mice gave similar results, i.e. aggregations of leucocytes and intravascular cell accumulations in 4 out of 30 and 3 out of 30 tissue samples, respectively. This shows that potent chemotactic factors such IL-1 alpha and FMLP administered in the early supravital period can induce moderate local leucocyte reactions in animal models in at least some cases. A clear morphological differentiation between vital and supravital chemotaxis does not seem to be possible. The supravitally stimulated accumulations of leucocytes are interpreted as an aggregation of resident macrophages in combination with a slight migration of blood leucocytes. Presumably, these alterations are restricted to the very early supravital period as long as sufficient energy reserves are available. It must be stated that the observed changes are reactions, not spontaneous actions, so that the general validity of the phenomenon of leucocyte infiltration as a vital parameter is not affected.