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 durin g 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 alp ha) 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) witho ut effective components was administered to equivalent areas of the an imals as a control. Tissue specimens were collected at 6 h postmortem (mice) and 12-14 h postmortem (pigs), cut into serial sections, staine d with H&E and examined under the microscope. A leucocyte reaction did not develop in pigs (n = 10, 30 tissue samples) following injection o f FMLP, however, dermal, subcutaneous and perivascular infiltration of leucocytes (in particular mononuclear cells and a few granulocytes) w as found in 3 out of 30 tissue specimens in murine experiments. In add ition intravascular cell accumulations were detected in 2 out 30 sampl es. The injection of IL-1 alpha to mice gave similar results, i.e. agg regations of leucocytes and intravascular cell accumulations in 4 out of 30 and 3 out of 30 tissue samples, respectively. This shows that po tent 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 differe ntiation between vital and supravital chemotaxis does not seem to be p ossible. The supravitally stimulated accumulations of leucocytes are i nterpreted as an aggregation of resident macrophages in combination wi th a slight migration of blood leucocytes. Presumably, these alteratio ns are restricted to the very early supravital period as long as suffi cient energy reserves are available. It must be stated that the observ ed changes are reactions, not spontaneous actions, so that the general validity of the phenomenon of leucocyte infiltration as a vital param eter is not affected.