The Journal of Immunology, Vol 141, Issue 5 1670-1677, Copyright © 1988 by American Association of Immunologists

ARTICLES

Effect of cytokines on polymorphonuclear neutrophil infiltration in the mouse. Prostaglandin- and leukotriene-independent induction of infiltration by IL-1 and tumor necrosis factor

TJ Sayers, TA Wiltrout, CA Bull, AC Denn 3d, AM Pilaro and B Lokesh
Biological Carcinogenesis Development Program, NCI-FCRF, Frederick, MD 21701-1013.

The i.p. injection of mice with highly purified recombinant human rIL-1 alpha or beta resulted in the rapid influx of a large number of polymorphonuclear neutrophils (PMN) into the peritoneal cavity. Significant increases in the number of PMN were induced by doses of IL- 1 which ranged from 0.005 to 5 ng/injection. Interestingly the dose response for PMN influx was bell-shaped because 50 ng of IL-1 did not result in a significant increase in peritoneal PMN. IL-1 induced PMN infiltration was detectable by 1 h with peak levels of PMN obtained by about 2 h, followed by a subsequent decline by 24 h. Other cytokines, IL-2, IFN-gamma, IFN alpha beta, granulocyte-CSF, granulocyte- macrophage-CSF, IL-3, TNF-alpha, and TNF-beta were compared to IL-1 for their ability to induce a PMN influx into the peritoneum. Only TNF- alpha or TNF-beta (lymphotoxin) were able to induce a significant influx of PMN within 2 h. However, based on total protein administered, about 100 times more TNF than IL-1 was required to produce a comparable PMN infiltration. Intraperitoneal injection of inhibitors of the cyclooxygenase or lipoxygenase pathways did not inhibit the IL-1- induced influx of PMN. Also, neither IL-1 nor TNF triggered an increase in PG or leukotriene release from peritoneal cells in vitro. Furthermore, direct peritoneal injection of leukotriene B4, a potent PMN chemoattractant in vitro, did not induce any significant increase in PMN in the peritoneal cavity indicating that chemotactic activity alone is insufficient for inducing peritoneal infiltration. These results suggest that the local production of very low levels of IL-1 in vivo would be sufficient to initiate a sequence of events that results in a rapid accumulation of PMN. Because IL-1 was not chemotactic for PMN in vitro, our data suggest that IL-1 induces production of factors that are chemotactic for PMN. Alternatively, IL-1 may act on other stages of the complex sequence of events that regulates the emigration of PMN into tissue sites in vivo. The synergy apparent in PMN influx when suboptimal concentrations of IL-1 and TNF were injected suggests that the local production of very low concentrations of these cytokines in situ could play a critical role in the emigration of PMN during infection.

This article has been cited by other articles:

				T. Eigenbrod, J.-H. Park, J. Harder, Y. Iwakura, and G. Nunez Cutting Edge: Critical Role for Mesothelial Cells in Necrosis-Induced Inflammation through the Recognition of IL-1{alpha} Released from Dying Cells J. Immunol., December 15, 2008; 181(12): 8194 - 8198. [Abstract] [Full Text] [PDF]

				K. D. McCall-Culbreath, Z. Li, and M. M. Zutter Crosstalk between the {alpha}2{beta}1 integrin and c-met/HGF-R regulates innate immunity Blood, April 1, 2008; 111(7): 3562 - 3570. [Abstract] [Full Text] [PDF]

				M. N. Ballinger, D. M. Aronoff, T. R. McMillan, K. R. Cooke, K. Olkiewicz, G. B. Toews, M. Peters-Golden, and B. B. Moore Critical Role of Prostaglandin E2 Overproduction in Impaired Pulmonary Host Response following Bone Marrow Transplantation J. Immunol., October 15, 2006; 177(8): 5499 - 5508. [Abstract] [Full Text] [PDF]

				C. Di Filippo, F. Rossi, S. Rossi, and M. D'Amico Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN J. Leukoc. Biol., March 1, 2004; 75(3): 453 - 459. [Abstract] [Full Text] [PDF]

				T. Cao, E. Pinter, S. Al-Rashed, N. Gerard, J. R. Hoult, and S. D. Brain Neurokinin-1 Receptor Agonists Are Involved in Mediating Neutrophil Accumulation in the Inflamed, But Not Normal, Cutaneous Microvasculature: An In Vivo Study Using Neurokinin-1 Receptor Knockout Mice J. Immunol., May 15, 2000; 164(10): 5424 - 5429. [Abstract] [Full Text] [PDF]

				U. Deiters and P. F. Muhlradt Mycoplasmal Lipopeptide MALP-2 Induces the Chemoattractant Proteins Macrophage Inflammatory Protein 1alpha (MIP-1alpha ), Monocyte Chemoattractant Protein 1, and MIP-2 and Promotes Leukocyte Infiltration in Mice Infect. Immun., July 1, 1999; 67(7): 3390 - 3398. [Abstract] [Full Text] [PDF]

				K.-i. Seino, K. Iwabuchi, N. Kayagaki, R. Miyata, I. Nagaoka, A. Matsuzawa, K. Fukao, H. Yagita, and K. Okumura Cutting Edge: Chemotactic Activity of Soluble Fas Ligand Against Phagocytes J. Immunol., November 1, 1998; 161(9): 4484 - 4488. [Abstract] [Full Text] [PDF]

				R. B. Vinson, J. L. Carroll, and S. B. Pruett Mechanism of suppressed neutrophil mobilization in a mouse model for binge drinking: role of glucocorticoids Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R1049 - R1057. [Abstract] [Full Text] [PDF]

				N. Pejnovic, D. Lilic, G. Zunic, M. Colic, M. Kataranovski, and A. Dujic Aberrant Levels of Cytokines Within the Healing Wound After Burn Injury Arch Surg, September 1, 1995; 130(9): 999 - 1006. [Abstract] [PDF]

				Y. Shi, S. J. Ullrich, J. Zhang, K. Connolly, K. J. Grzegorzewski, M. C. Barber, W. Wang, K. Wathen, V. Hodge, C. L. Fisher, et al. A Novel Cytokine Receptor-Ligand Pair. IDENTIFICATION, MOLECULAR CHARACTERIZATION, AND IN VIVO IMMUNOMODULATORY ACTIVITY J. Biol. Chem., June 16, 2000; 275(25): 19167 - 19176. [Abstract] [Full Text] [PDF]