0192-0561/90 $3.00 + .00 Pergamon Press plc International Society for lmmunopharmacology.
Int. J. lmmunopharmac., Vol. 12, No. 6, pp. 605-611, 1990. Printed in Great Britain.
INTERLEUKIN-2 INCREASES THE OXIDATIVE ACTIVITY AND INDUCES MIGRATION OF MURINE POLYMORPHONUCLEAR LEUKOCYTES IN VIVO* PAUL STEVENSt and DUANE E. PIAZZA Cetus Corporation, 1400 Fifty-third Street, Emeryville, CA 94608, U.S.A. (Received 24 July 1989 and in final form 5 March 1990)
Abstract - - Since recombinant human interleukin-2 (IL-2) can protect mice from a lethal bacterial challenge
and can induce a vascular leak, we investigated the effects of IL-2 on the oxidative metabolism and migration of murine polymorphonuclear leukocytes (PMN) in vivo. To assess oxidative activity of PMN, we used luminol-dependent chemiluminescence (CL) to measure oxygen radical formation after stimulation of the PMN with phorbol myristate acetate (PMA). We demonstrated that single IP doses of IL-2, from 0 . 2 - 3 mg/kg, could significantly increase CL from peripheral blood PMN obtained after IL-2 treatment. The increase of PMN-CL induced by IL-2 in vivo reached a maximum 4.5 fold increase at 3 and 6 h after IL-2 treatment. At 1, 12, and 24 h after rlL-2 treatment, there were no changes in CL and PMN activity remained within normal limits. Intraperitoneally administered IL-2 also caused a significant influx of PMN into the peritoneal cavity. IL-2 increased the percentage of PMN among the peritoneal exudate cells from a control baseline level of < 1070to 18°70PMN after IL-2 treatment. These data that demonstrate the capacity of IL-2 to augment the function and metabolism of PMN in vivo and illustrates the broad range of effects of IL-2 on the immune system in vivo and may explain in part the protective effects of IL-2 in experimental bacterial infections and the possible role of PMN in the systemic toxicities induced by IL-2.
Interleukin-2 (IL-2) is a glycoprotein h o r m o n e that was originally described as an in vitro growth factor for T-lymphocytes (Morgan, Ruscetti & Gallo, 1976). IL-2 has also been shown to enhance natural killer cell activity (Rosenberg, Speiss & Schwartz, 1983) and generate lymphocyte activated killer cells from resting lymphocytes (Lotze, Grimm, M a z u m d e r , Strausser & Rosenberg, 1981). A l t h o u g h primarily considered as a cytokine that can augment lymphocyte function, recent reports have demonstrated that IL-2 can increase the cytotoxicity (Malkovsky, Loveland, North, Asherson, Gao, W a r d & Fiers, 1987) and microbicidal activity (Wahl, McCartney-Frances, H u n t , Smith, Wahl & Katona, 1987) of h u m a n monocytes. Because recent studies continue to show that IL-2 has a much broader spectrum of activity on cells of the immune system including macrophages, we were interested to investigate the possible effects of IL-2
on polymorphonuclear neutrophils (PMN) function. The study of IL-2 on P M N function is important f r o m two perspectives. First, IL-2 had been previously shown to protect mice from a lethal challenge of G r a m negative bacteria (Chong, 1987) and second, IL-2 can induce systemic toxicities that involve an inflammatory response that includes a vascular leak (Lotze, Matory, Raynor, Ettinghaussen, Seipp & Rosenberg, 1986) and a syndrome similar to septic shock (Ognibene, Rosenberg, Lotze, Skibber, Parker, Shelhammer & Parillo, 1988). Since P M N have a major part in the cellular host defense against Gram-negative bacterial infection and an important role in the inflammatory response, we report on the capacity of IL-2 to (1) increase the oxidative activity of murine P M N as measured by luminol-dependent chemiluminescence (CL), and (2) elicit migration of P M N in vivo.
*Presented in part as an abstract Federation Proceedings Abstract#8032 p. 301 (1988) tTo whom correspondence should be addressed at present address: Amgen Department of Pharmacology, Amgen Center, Thousand Oaks, CA 91320, U.S.A. 605
606
P. STEVENSand D. E. PIAZZA MATERIALS
We used highly purified recombinant human interleukin-2 (IL-2) derived from E. coli (Wang, Lu & Mark, 1984) (Cetus Corporation) that contained
Int. J. lmmunopharmac., Vol. 12, No. 6, pp. 605-611, 1990. Printed in Great Britain.
INTERLEUKIN-2 INCREASES THE OXIDATIVE ACTIVITY AND INDUCES MIGRATION OF MURINE POLYMORPHONUCLEAR LEUKOCYTES IN VIVO* PAUL STEVENSt and DUANE E. PIAZZA Cetus Corporation, 1400 Fifty-third Street, Emeryville, CA 94608, U.S.A. (Received 24 July 1989 and in final form 5 March 1990)
Abstract - - Since recombinant human interleukin-2 (IL-2) can protect mice from a lethal bacterial challenge
and can induce a vascular leak, we investigated the effects of IL-2 on the oxidative metabolism and migration of murine polymorphonuclear leukocytes (PMN) in vivo. To assess oxidative activity of PMN, we used luminol-dependent chemiluminescence (CL) to measure oxygen radical formation after stimulation of the PMN with phorbol myristate acetate (PMA). We demonstrated that single IP doses of IL-2, from 0 . 2 - 3 mg/kg, could significantly increase CL from peripheral blood PMN obtained after IL-2 treatment. The increase of PMN-CL induced by IL-2 in vivo reached a maximum 4.5 fold increase at 3 and 6 h after IL-2 treatment. At 1, 12, and 24 h after rlL-2 treatment, there were no changes in CL and PMN activity remained within normal limits. Intraperitoneally administered IL-2 also caused a significant influx of PMN into the peritoneal cavity. IL-2 increased the percentage of PMN among the peritoneal exudate cells from a control baseline level of < 1070to 18°70PMN after IL-2 treatment. These data that demonstrate the capacity of IL-2 to augment the function and metabolism of PMN in vivo and illustrates the broad range of effects of IL-2 on the immune system in vivo and may explain in part the protective effects of IL-2 in experimental bacterial infections and the possible role of PMN in the systemic toxicities induced by IL-2.
Interleukin-2 (IL-2) is a glycoprotein h o r m o n e that was originally described as an in vitro growth factor for T-lymphocytes (Morgan, Ruscetti & Gallo, 1976). IL-2 has also been shown to enhance natural killer cell activity (Rosenberg, Speiss & Schwartz, 1983) and generate lymphocyte activated killer cells from resting lymphocytes (Lotze, Grimm, M a z u m d e r , Strausser & Rosenberg, 1981). A l t h o u g h primarily considered as a cytokine that can augment lymphocyte function, recent reports have demonstrated that IL-2 can increase the cytotoxicity (Malkovsky, Loveland, North, Asherson, Gao, W a r d & Fiers, 1987) and microbicidal activity (Wahl, McCartney-Frances, H u n t , Smith, Wahl & Katona, 1987) of h u m a n monocytes. Because recent studies continue to show that IL-2 has a much broader spectrum of activity on cells of the immune system including macrophages, we were interested to investigate the possible effects of IL-2
on polymorphonuclear neutrophils (PMN) function. The study of IL-2 on P M N function is important f r o m two perspectives. First, IL-2 had been previously shown to protect mice from a lethal challenge of G r a m negative bacteria (Chong, 1987) and second, IL-2 can induce systemic toxicities that involve an inflammatory response that includes a vascular leak (Lotze, Matory, Raynor, Ettinghaussen, Seipp & Rosenberg, 1986) and a syndrome similar to septic shock (Ognibene, Rosenberg, Lotze, Skibber, Parker, Shelhammer & Parillo, 1988). Since P M N have a major part in the cellular host defense against Gram-negative bacterial infection and an important role in the inflammatory response, we report on the capacity of IL-2 to (1) increase the oxidative activity of murine P M N as measured by luminol-dependent chemiluminescence (CL), and (2) elicit migration of P M N in vivo.
*Presented in part as an abstract Federation Proceedings Abstract#8032 p. 301 (1988) tTo whom correspondence should be addressed at present address: Amgen Department of Pharmacology, Amgen Center, Thousand Oaks, CA 91320, U.S.A. 605
606
P. STEVENSand D. E. PIAZZA MATERIALS
We used highly purified recombinant human interleukin-2 (IL-2) derived from E. coli (Wang, Lu & Mark, 1984) (Cetus Corporation) that contained
