Immuno-modulation and anti-inflammatory benefits of antibiotics: The example of tilmicosin

Canadian Journal of Veterinary Research

Volumn 74, Issue 1, 2010, Pages 1-10

  Buret, André G ^a  

^a UNIVERSITY OF CALGARY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; AZITHROMYCIN; BETA2 INTEGRIN; CAMPTOTHECIN; CD11B ANTIGEN; CEFTIOFUR; CLARITHROMYCIN; CYTOKINE; DEXAMETHASONE; DIRITHROMYCIN; ENDOTHELIN 1; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; ERYTHROMYCIN; FISH OIL; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; LEUKOTRIENE B4; MACROLIDE; MESSENGER RNA; OXYTETRACYCLINE; PENICILLIN G; PROSTAGLANDIN E2; ROXITHROMYCIN; TILMICOSIN; TULATHROMYCIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ACTINOBACILLUS; ANIMAL HEALTH; ANTIBACTERIAL ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BACTERIAL PNEUMONIA; CANCER CELL; CARCASS; CATTLE DISEASE; CELL FUNCTION; CYTOKINE PRODUCTION; DEATH; DOSE RESPONSE; DRUG EFFICACY; DRUG MECHANISM; DRUG PENETRATION; DRUG UPTAKE; ELASTOLYSIS; ENDOCRINE SYSTEM; FOOD INDUSTRY; FOOD INTAKE; GENE EXPRESSION; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LUNG ALVEOLUS MACROPHAGE; LUNG INSUFFICIENCY; LUNG LAVAGE; MASTITIS; METABOLISM; MILK PRODUCTION; MODEL; MYCOPLASMA; NERVOUS SYSTEM; NEUTROPHIL; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PASTEURELLA; PORCINE PLEUROPNEUMONIA; REPRODUCTION; RESPIRATORY BURST; RESPIRATORY TRACT INFECTION; REVIEW; STREPTOCOCCUS PNEUMONIAE; TH1 CELL; TH2 CELL;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTI-INFLAMMATORY AGENTS; APOPTOSIS; HUMANS; IMMUNOMODULATION; NEUTROPHILS; TYLOSIN;

ANIMALIA;

EID: 75649089658     PISSN: 08309000     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (105)

1. Husband AJ. The immune system and integrated homeostasis. Immunol Cell Biol 1995;73:377-382.
2. Kenison DC, Elsasser TH, Fayer R. Tumor necrosis factor as a potential mediator of acute metabolic and hormonal responses to endotoxemia in calves. Am J Vet Res 1991;52:1320-1326.
3. Axelrod J, Reisine TD. Stress hormones: Their interactions and regulation. Science 1984;224:452-459.
4. Buret AG. How stress induces intestinal hypersensitivity. Am J Pathol 2006;168:3-5.
5. Roth JA, Perino LJ. Immunology and prevention of infection in feedlot cattle. Vet Clin N Am Food Anim Pract 1998;14:233-256.
6. Fair JM, Hansen ES, Ricklefs RE. Growth development stability and immune response in juvenile Japanese quails. Proc R Soc Lond B 1999;266:1735-1742.
7. Hansen SA, Hasselquist D, Folstad I, Eridstad KE. Costs of immunity: Immune responsiveness reduces survival of a vertebrate. Proc R Soc Lond B Biol Sci 2004;271:925-930.
8. Norris K, Evans MR. Ecological immunology: Life history trade-offs and immune defense in birds. Behav Ecol 2000;11: 19-26.
9. Pilorz V, Jaeckel M, Knudsen K, Trillich F. The cost of specific immune response in young guinea pigs. Physiol Behav 2005; 85:205-211.
10. Horak P, Ots I, Tegelmann L, Moller AP. Health impact of phytoaemagglutinin-induced immune challenge on great tit nestlings. Can J Zool 2000;78:905-910.
11. Nockels CF. Mineral alterations associated with stress, trauma, and infection, and the effects on immunity. The Compendium 1990;12:1133-1139.
12. Hurley BP, McCormick BA. Multiple roles of phospholipase A2 during lung infection and inflammation. Infect Immun 2008;76(6):2259-2272.
13. Korver DR, Klasing KC. Dietary fish oil alters specific and inflammatory immune responses in chicks. J Nutr 1997;127: 2039-2046.
14. Liu YL, Li DF, Gong LM, Yi GF, Gaines AM, Carroll JA. Effects of fish oil supplementation on the performance and the immuno logical, adrenal, and somatotropic responses of weaned pigs after and Escherichia coli lipopolysaccharide challenge. J Anim Sci 2003;81:2758-2765.
15. Klasing KC. Protecting animal health and well-being: Nutrition and immune function. In: Recent advances in animal nutrition, Garnsworthy RC, Wiseman J, eds., Nottingham Univer Pr, 2005, pp 13-20.
16. Tracey KL, Wei H, Manogue K, et al. Cachetin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 1988;167:1211-1227.
17. Boisclair YR, Wang J, Shi J, Hurst KR, Oi GT. Role of the suppressor of cytokine signaling-3 in mediating the inhibitory effects of interleukin-1 beta on the growth hormone-dependent transcription of the acid-labile subunit gene in liver cells. J Biol Chem 2000;275:3841-3847.
18. Johnson RW. Inhibition of growth by pro-inflammatory cytokines: An integrated view. J Anim Sci 1997;75:1244-1255.
19. Gabler NK, Spurlock E. Intergrating the immune system with the regulation of growth and efficiency. J Anim Sci 2008; 86(E. Suppl.):E64-E74.
20. Klasing KC, Johnstone BJ. Monokines in growth and development. Poult Sci 1991;70:1781-1789.
21. Waldhorn MR, Overton TR. Effects of inflammation on nutrition: Is sickness causing weakness in your diet? In: 21st Ann SW Nutr and Manag Conf, Tempe, Arizona, USA. 2006: 164-173.
22. Burciaga-Robles LO, Step DL, Holland BP, et al. Effects of an intratracheal Mannheimia haemolytica challenge on intake and nitrogen balance in fed and fasted steers. 2006. [page on Internet]. Available from http://www.ansi.okstate.edu/ research/ Last accessed 23 July, 2009.
23. Walker RD, Hopkins FM, Schultz TW, McCracken MD, Moore RN. Changes in leukocyte populations in pulmonary lavage fluids of calves after inhalation of Pasteurella haemolytica. Am J Vet Res 1985;46:2429-2433.
24. Yoo HS, Maheswaran SK, Lin G, Townsend EL, Ames TR. Induction of inflammatory cytokines in bovine alveolar macrophages following stimulation with Pasteurella haemolytica lipopolysaccharide. Infect Immun 1995;63:381-388.
25. Tsai KS, Grayson MH. Pulmonary defense mechanisms against pneumonia and sepsis. Curr Op Pulm Med 2008;14:260-265.
26. Paape MJ, Bannerman DD, Zhao X, Lee JW. The bovine neutrophil: Structure and function in blood and milk. Vet Res 2003;34:597-627.
27. Squier MKT, Shenert AJ, Cohen JJ. Apoptosis in leukocytes. J Leukoc Biol 1995;57:2-10.
28. Henson PM, Johnston RB. Tissue injury in inflammation: Oxidants, proteinases, and cationic proteins. J Clin Invest 1987; 79:669-678.
29. Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, Haslett C. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J Clin Invest 1989;83: 865-875.
30. Cox GJ, Crossely J, Xing Z. Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. Am J Respir Cell Mol Biol 1995;12: 232-237.
31. Lechtenberg KR, Shryock TR, Moore GM. Characterization of an Actinobacillus pleuropneumoniae seeder pig challenge-exposure model. Am J Vet Res 1994;55:1703-1709.
32. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239-257.
33. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatydilserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 1992;148:2207-2216.
34. Morris RG, Hargreaves AD, Duvall E, Wyllie AH. Hormone-induced cell death. II Surface changes in thymocytes undergoing apoptosis. Am J Pathol 1984;115:426-430.
35. Dransfield I, Buckle AM, Savill JS, McDowall A, Haslett C, Hogg N. Neutrophil apoptosis is associated with a reduction in CD16 expression. J Immunol 1994;153:1254-1260.
36. Haslett C. Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med 1999;160:S5-S11.
37. Hughes J, Liu Y, VanDamme J, Savill J. Human glomerular mesangial cell phagocytosis of apoptotic neutrophils: Mediation by a novel CD36-independent vitronectin receptor/ thrombospondin recognition mechanism that is uncoupled from chemokine secretion. J Immunol 1997;158:4389.
38. Hart SP, Ross JA, Ross K, Haslett C, Dransfield I. Molecular characterization of the surface of apoptotic neutrophils: Implications for functional deregulation and recognition by phagocytes. Cell Death Differ 2000;7:493-499.
39. Takizawa F, Tsuji S, Nagasawa S. Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells. FEBS Lett 1996;397:269-275.
40. Mevorach D, Mascarenhas JO, Gershow D, Elkon KB. Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 1998;188:2313.
41. Ren Y, Stuart L, Lindberg FP, et al. Nonphlogistic clearance of late apoptotic neutrophils by macrophages: Efficient phagocytosis independent of b2 integrins. J Immunol 2001;166: 4743-4750.
42. Schagat TL, Wofford JA, Wright JR. Surfactant Protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils. J Immunol 2001;166:2727-2733.
43. Savill J. Apoptosis in resolution of inflammation. J Leukocyte Biol 2000;61:375.
44. Savill J, Fadok VA. Corpse clearance defines the meaning of cell death. Nature 2000;407:784-788.
45. Meagher LC, Savill JS, Baker A, Fuller RW, Haslett C. Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2. J Leukocyte Biol 1992;52: 269-276.
46. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 1998;101:890-899.
47. Godson C, Mitchell S, Harvey K, Petasis NA, Hogg N, Brady HR. Cutting edge: Lipoxins rapidly stimulate nonphlogisitc phagocytosis of apoptotic neutrophils by monocytederived macrophages. J Immunol 2000;164:1663-1667.
48. Fadok VA, Bratton DL, Guthrie L, Henson PM. Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: Role of proteases. J Immunol 2001;166:6847-6854.
49. Gilroy DW. Inflammatory resolution: New opportunities for drug discovery. Nature Rev Drug Discov 2004;3:401-416.
50. Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD. Resolvin E1 regulates interleukin 23, interferon-gamma, and lipoxin A4 to promote the resolution of allergic airway inflammation. Nature Immunol 2008;9:873-879.
51. Schwab JM, Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007;447:869-874.
52. Serhan CN, Brain SD, Buckley CD, et al. Resolution of inflammation: State of the art, definitions and terms. FASEB Journal 2007;21:325-332.
53. Rossi AG, Hallett JM, Sawatzky DA, Teixeira MM, Haslett C. Modulation of granulocyte apoptosis can influence the resolution of inflammation. Biochem Soc Trans 2007;35:288-291.
54. Hallett JM, Leitch AE, Riley NA, Duffin R, Haslett C, Rossi AG. Novel pharmacological strategies for driving inflammatory cell apoptosis and enhancing the resolution of inflammation. Trends Pharmacol Sci 2008;29:250-257.
55. Rossi AG, Sawatzky DA, Walker A, et al. Cyclin-dependent kinases inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nature Med 2006; 12:1056-1064.
56. Labro MT. Anti-inflammatory activity of macrolides: A new therapeutic potential? J Antimicrob Chemother 1998;41(Suppl.B):37-46.
57. Wales D, Woodhead M. The anti-inflammatory effects of macrolides: Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells. Thorax 1999;54(Suppl.2):S58-S62.
58. Ianaro A, Ialenti A, Maffia P, et al. Anti-inflammaotry activity of macrolide antibiotics. J Pharmacol Exp Therapeut 2000;292: 156-163.
59. Rubin BK, Tamaoki J. Macrolide antibiotics as biological response modifiers. Curr Op Invest Drugs 2000;1:169-172.
60. Cervin A. The anti-inflammatory effects of erythromycin and its derivatives, with special reference to nasal polyposis and chronic sinusitis. Acta Otolaryngol 2001;121:83-92.
61. Azuma A. Roles of macrolides in treatment of lung injury. In: Parnham MJ, Rubin BK, Tamaoki J, eds. Antibiotics as Anti-inflammatory and Immunomodulatry Agents. Basel: Birkhaeuser (Basel, Springer), 2005:219-226.
62. Peeters TL. Erythromycin and other macrolides as prokinetic agents. Gastroenterology 1993;105:1886-1899.
63. Mikasa K, Sawaki M, Kita E, et al. Significant survival benefits to patients with advanced non-small-cell lung cancer from treatment with clarithromycin. Chemotherapy 1997;43: 288-296.
64. Yatsunami J, Fukuno Y, Nagat M, et al. Antiangiogenic and antitumor effects of 14-membered macrolides on mouse B16 melanoma cells. Clin Exp Metastasis 1999;17:361-367.
65. Rubin BK, Druce H, Ramirez OE, Palmer R. Effect of clarithromycin on nasal mucus properties in healthy subjects and in patients with purulent rhinitis. Am J Respir Crit Care Med 1997;155:2018-2023.
66. Tamaoki J, Takemyama K, Yamawaki I, Kondo M, Konno K. Lipopolysaccharide-induced goblet cell hypersecretion in the guinea pig trachea: Inhibition by macrolides. Am J Physiol 1997;272:L15-L19.
67. Woo PC, Tsoi HW, Wong LP, Leung HC, Yuen KY. Antibiotics modulate vaccine-induced humoral immune response. Clin Diagn Lab Immunol 1999;6:832-837.
68. Sassa K, Mizushima Y, Kobayashi M. Differential modulatory effects of clarithromycin on the production of cytokines by a tumor. Antimicrob Agents Chemother 1999;43:2787-2789.
69. Aoshiba K, Nagai A, Konno K. Erythromycin shortens neutrophil survival by accelerating apoptosis. Antimicrob Ag Chemother 1995;39:872-877.
70. Inamura K, Ohta N, Fukaze S, Kasajima N, Aoyagi M. The effects of erythromycin on human peripheral neutrophil apoptosis. Rhinology 2000;38:124-129.
71. Fisher CD, Zvaigzne C, Morck DW, Lucas MJ, Robb EJ, Buret AG. Tulathromycin inhibits NF-kB signaling and induces apoptosis in bovine neutrophils in caspase-3-dependent fashion. FASEB J 2008;22:lb591.
72. Scorneaux B, Shryock TR. Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in bovine mammary, blood, and lung cells. J Dairy Sc 1999;82:1202-1212.
73. Bonnet M, van der Auwera P. In vitro and in vivo intraleukocytic accumulation of azithromycin (CP-62,993). Antimicrob Ag Chemother 1992;36:1302-1309.
74. Koch CC, Esteban DJ, Chin AC, et al. Apoptosis, oxidative metabolism and interleukin-8 production in human neutrophils exposed to azithromycin: Effects of Streptococcus pneumoniae. J Antimicrob Chemother 2000;46:19-26.
75. Khair OA, Devalia JL, Abdelaziz MM. Effects of erythromycin on H. influenzae endotoxin-induced release of IL-6, IL-8, and sICAM-1 by cultured human bronchial epithelial cells. Eur Respir J 1995;8:1451-1457.
76. Gorham PE, Carroll LH, McAskill JW. Tilmicosin as a single injection treatment for respiratory disease of feedlot cattle. Can J Vet Res 1990;31:826-829.
77. Moore GM, Mowrey DH, Tonkinson LV, Lechtenberg KF, Schneider JH. Efficacy dose determination study of tilmicosin phosphate in feed for control of pneumonia caused by Actinobacillus pleuropneumoniae in swine. Am J Vet Res 1996;57:220-223.
78. Jordan WH, Byrd RA, Cochrane RL. A review of the toxicology of the antibiotic Micotil 300. Vet Hum Toxicol 1993;35: 151-158.
79. Morck DW, Merrill JK, Gard MS. Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin. Can J Vet Res 1997;61:187-192.
80. Moore GM, Basson RP, Tonkinson LV. Clinical field trials with tilmicosin phosphate in feed for the control of naturally acquired pneumonia caused by Actinobacillus pleuropneumoniae and Pasteurella multocida in swine. Am J Vet Res 1996;57:224-227.
81. Diarra MS, Malouin F, Jacques M. Postantibiotic and physiological effects of tilmicosin, tylosin, and apramycin at subminimal and suprainhibitory concentrations on some swine and bovine respiratory tract pathogens. Int J Antimicrob Ag 1999;12:229-237.
82. Chin A, Morck DW, Merrill JK, et al. Anti-inflammatory benefits of tilmicosin in calves with P. haemolytica-infected lungs. Am J Vet Res 1998;59:765-771.
83. Chin A, Lee WD, Murrin KA, et al. Tilmicosin induces apoptosis in bovine neutrophils in the presence or in the absence of P. haemolytica and promotes neutrophil phagocytosis by macrophages. Antimicrob Ag Chemother 2000;44:2465-2470.
84. Lee WD, Flynn AN, LeBlanc JM, et al. Tilmicosin-induced bovine neutrophil apoptosis is cell-specific and downregulates spontaneous LTB4 synthesis without increasing Fas expression. Vet Res 2004;35:213-224.
85. Lakritz J, Tyler JW, Marsh AE, Romesburg-Cockrell M, Smith K, Holle JM. Tilmicosin reduces lipopolysaccharide-stimulated bovine alveolar macrophage prostaglandin E(2) production via a mechanism involving phospholipases. Vet Ther 2002;3:7-21.
86. Weinhold U, Hofmann W, Mulling C, Budras KD. Untersuchungen von Bronchialzellsedimenten lungenkranker Kaelber waehrend der Behandlung mit den Antibiotika Tilmicosin und Ceftiofur auf das Vorkommen der Apoptosis der neutrophilen Granulozyten, Tieraerztl. Unschau 2003;58:191-199.
87. Fajt VR, Apley MD, Roth JA, et al. The effects of danofloxacin and tilmicosin on neutrophil function and lung consolidation in beef heifer calves with induced Pasteurella (Mannheimia) haemolytica pneumonia, J Vet Pharmacol Therap 2003;26: 173-179.
88. 4, and attenuates inflammation in the Actinobacillus pleuropneumoniae-Infected Porcine Lung. Am J Vet Res 2005;66:100-107.
89. Cao XY, Dong M, Shen JZ, et al. Tilmicosin and tylosin have anti-inflammatory properties via modulation of COX-2 and iNOS gene expression and production of cytokines in LPS-induced macrophages and monocytes. Int J Antimicrob Ag 2006;27:431-438.
90. Reuter RR, Carroll JA, Dailey JW, Cook BJ, Galyean ML. Effects of dietary energy source and level and injection of tilmicosin phosphate on immune function in lipopolysaccharide-challenged beef steers. J Anim Sci 2008 (April 11; epub ahead of print).
91. Levert H, Gressier B, Brunte C, et al. Time and concentration dependent influence of dirithromycin on neutrophils oxidative burst. J Antibiot 1999;52:127-133.
92. Kanota JI, Iwashita T, Matsubara Y, et al. Inhibitory effect of erythromycin on superoxide anion production by human neutrophils primed with granulocyte-colony stimulating factor. Antimicrob Ag Chemother 1998;42(7):1866-1867.
93. Lin HC, Wang CH, Liu CY, Yu CT, Kuo HP. Erythromycin inhibits β2-integrins (CD11b/CD18) expression, interleukin-8 release and intracellular oxidative metabolism in neutrophils. Respir Med 2000;94:654-660.
94. Takisawa H, Desaki M, Ohtoshi T. Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells. Eur Respir J 1998;12:57-63.
95. Frost RA, Nystrom GJ, Lang CH. Lipopolysaccharide regulates pro-inflammatory cytokine expression in mouse myofibroblasts and skeletal muscle. Am J Physiol Integr Comp Physiol 2002;283:R698-R709.
96. Schrick FN, Hockett ME, Saxton AM, Lewis MJ, Dowlen HH, Oliver SP. Influence of subclinical mastitis during early lactation on reproductive parameters. J Dairy Sci 2001;84:1407-1412.
97. Hockett ME, Hopkins FM, Lewis MJ, et al. Endocrine profiles of dairy cows following experimentally induced clinical mastitis during early lactation. Anim Reprod Sci 2000;58:241-251.
98. Rajala-Schultz PJ, Grohn YT, McCulloch CE, Guard CL. Effects of clinical mastitis on milk yield in dairy cows. J Dairy Sci 1999;82:1213-1220.
99. Shuster DE, Kehrli ME, Baumrucker CR. Relationship of inflammatory cytokines, growth hormone, and insulin-like growth factor-1 to reduced performance during infectious disease. Proc Soc Exp Biol Med 1995;210:140-149.
100. Miyanohara T, Ushikai M, Matsune S, Ueno K, Katahira S, Kurono Y. Effects of clarithromycin on cultured human nasal epithelial cells and fibroblasts. Laryngoscope 2000;110:126-131.
101. Kawasaki S, Takisawa H, Ohtoshi T. Roxithromycin inhibits cytokine production by and neutrophil attachment to human bronchial epithelial cells in vitro. Antimicrob Ag Chemother 1998;42:1499-1502.
102. Fujita K, Shimizu T, Majima Y, Sakakura Y. Effects of macrolides on interleukin-8 secretion from human nasal epithelial cells. Eur Arch Otorhinolaryngol 2000;257:199-204.
103. Schultz M, Speelman P, Zaat S. Erythromycin inhibits TNFalpha and IL-6 production induced by heat-killed S. pneumoniae in whole blood. Antimicrob Ag Chemother 1998;42:1605-1609.
104. Schultz MJ, Speelman P, Hack CE, Buurman WA, van Deventer SJH, van der Poll T. Intravenous infusion of erythromycin inhibits CXC chemokine production, but augments neutrophil degranulation in whole blood stimulated with S. pneumoniae. J Antimicrob Ag Chemother 2000;46:235-240.
105. Ichikawa Y, Ninomiya H, Koga H. Erythromycin reduces neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. Am Rev Resp Dis 1992;146: 196-203.