Lidocaine inhibits granulocyte adherence and prevents granulocyte delivery to inflammatory sites

Abstract

Incubation of whole blood or polymorphonuclear leukocytes (PMNs) in saline with 10-2 or 10-4 molar concentations of lidocaine causes a reversible inhibition of granulocyte adherence. A single bolus dose of lidocaine, 2.5 mg/kg, given intravenously inhibits adherence in rabbits by 55.4% at 5 min, with return to normal by 15 min after dose. When the bolus dose is followed by an infusion of lidocaine, 0.3 mg/kg/min, adherence stays at less than 50% of control values for the duration of the infusion. Plasma from animals given lidocaine inhibits adherence of normal granulocytes, and the inhibiting factor is removed completely by dialysis of the plasma against modified Hanks' solution for 24 hr. Lidocaine infusion prevents delivery of PMNs to sites of inflammation: normal rabbits given sterile peritonitis developed exudates in 6 hr containing a mean of 19,280 PMN/cu mm compared to 388/cu mm in lidocaine-infused rabbits (2% of control). By comparison, methylprednisolone-treated animals developed exudate PMN counts 40% of control. When peritonitis was induced by staphylococci, 5 of 6 lidocaine-infused animals died, whereas only 1 of 6 noninfused animals died. Pathologic examination of experimentally infected skin showed that control animals developed an inflammatory reaction characterized by edema and pronounced PMN filtration 12 hr after intracutaneous injection of five staphylococci. In contrast, biopsies from lidocaine-infused animals showed only edema, with virtually no PMN infiltration. Thus, lidocaine inhibits granulocyte adherence in vitro and in vivo and markedly suppresses delivery of PMNs to sites of inflammation.