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Environ Health Perspect. 1995 March; 103(Suppl 2): 77–89.
PMCID: PMC1518840
Research Article

The effects of ozone on immune function.

Abstract

A review of the literature reveals that ozone (O3) exposure can either suppress or enhance immune responsiveness. These disparate effects elicited by O3 exposure depend, in large part, on the experimental design used, the immune parameters examined as well as the animal species studied. Despite the apparent contradictions, a general pattern of response to O3 exposure can be recognized. Most studies indicate that continuous O3 exposure leads to an early (days 0-3) impairment of immune responsiveness followed, with continued exposures, by a form of adaptation to O3 that results in a re-establishment of the immune response. The effects of O3 exposure on the response to antigenic stimulation also depend on the time at which O3 exposure occurred. Whereas O3 exposure prior to immunization is without effect on the response to antigen, O3 exposure subsequent to immunization suppresses the response to antigen. Although most studies have focused on immune responses in the lung, numerous investigators have provided functional and anatomical evidence to support the hypothesis that O3 exposure can have profound effects on systemic immunity.

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Selected References

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  • Dziedzic D, White HJ. Thymus and pulmonary lymph node response to acute and subchronic ozone inhalation in the mouse. Environ Res. 1986 Dec;41(2):598–609. [PubMed]
  • Li AF, Richters A. Ambient level ozone effects on subpopulations of thymocytes and spleen T lymphocytes. Arch Environ Health. 1991 Jan-Feb;46(1):57–63. [PubMed]
  • Bleavins MR, Dziedzic D. An immunofluorescence study of T and B lymphocytes in ozone-induced pulmonary lesions in the mouse. Toxicol Appl Pharmacol. 1990 Aug;105(1):93–102. [PubMed]
  • Dziedzic D, White HJ. T-cell activation in pulmonary lymph nodes of mice exposed to ozone. Environ Res. 1986 Dec;41(2):610–622. [PubMed]
  • Osebold JW, Owens SL, Zee YC, Dotson WM, LaBarre DD. Immunological alterations in the lungs of mice following ozone exposure: changes in immunoglobulin levels and antibody-containing cells. Arch Environ Health. 1979 Jul-Aug;34(4):258–265. [PubMed]
  • Van Loveren H, Rombout PJ, Wagenaar SS, Walvoort HC, Vos JG. Effects of ozone on the defense to a respiratory Listeria monocytogenes infection in the rat. Suppression of macrophage function and cellular immunity and aggravation of histopathology in lung and liver during infection. Toxicol Appl Pharmacol. 1988 Jul;94(3):374–393. [PubMed]
  • Fujimaki H. Impairment of humoral immune responses in mice exposed to nitrogen dioxide and ozone mixtures. Environ Res. 1989 Apr;48(2):211–217. [PubMed]
  • Hassett C, Mustafa MG, Coulson WF, Elashoff RM. Splenomegaly in mice following exposure to ambient levels of ozone. Toxicol Lett. 1985 Aug;26(2-3):139–144. [PubMed]
  • Dziedzic D, Wright ES, Sargent NE. Pulmonary response to ozone: reaction of bronchus-associated lymphoid tissue and lymph node lymphocytes in the rat. Environ Res. 1990 Apr;51(2):194–208. [PubMed]
  • Eskew ML, Scheuchenzuber WJ, Scholz RW, Reddy CC, Zarkower A. The effects of ozone inhalation on the immunological response of selenium- and vitamin E-deprived rats. Environ Res. 1986 Aug;40(2):274–284. [PubMed]
  • Burleson GR, Keyes LL, Stutzman JD. Immunosuppression of pulmonary natural killer activity by exposure to ozone. Immunopharmacol Immunotoxicol. 1989;11(4):715–735. [PubMed]
  • Van Loveren H, Krajnc EI, Rombout PJ, Blommaert FA, Vos JG. Effects of ozone, hexachlorobenzene, and bis(tri-n-butyltin)oxide on natural killer activity in the rat lung. Toxicol Appl Pharmacol. 1990 Jan;102(1):21–33. [PubMed]
  • Savino A, Peterson ML, House D, Turner AG, Jeffries HE, Baker R. The effect of ozone on human cellular and humoral immunity: characterization of T and B lymphocytes by rosette formation. Environ Res. 1978 Feb;15(1):65–69. [PubMed]
  • Osebold JW, Gershwin LJ, Zee YC. Studies on the enhancement of allergic lung sensitization by inhalation of ozone and sulfuric acid aerosol. J Environ Pathol Toxicol. 1980 Jun-Jul;3(5-6):221–234. [PubMed]
  • Osebold JW, Zee YC, Gershwin LJ. Enhancement of allergic lung sensitization in mice by ozone inhalation. Proc Soc Exp Biol Med. 1988 Jul;188(3):259–264. [PubMed]
  • Gershwin LJ, Osebold JW, Zee YC. Immunoglobulin E-containing cells in mouse lung following allergen inhalation and ozone exposure. Int Arch Allergy Appl Immunol. 1981;65(3):266–277. [PubMed]
  • Matsumura Y. The effects of ozone, nitrogen dioxide, and sulfur dioxide on the experimentally induced allergic respiratory disorder in guinea pigs. II. The effects of ozone on the absorption and the retention of antigen in the lung. Am Rev Respir Dis. 1970 Sep;102(3):438–443. [PubMed]
  • Matsumura Y. The effects of ozone, nitrogen dioxide, and sulfur dioxide on the experimentally induced allergic respiratory disorder in guinea pigs. I. The effect on sensitization with albumin through the airway. Am Rev Respir Dis. 1970 Sep;102(3):430–437. [PubMed]
  • Ozawa M, Fujimaki H, Imai T, Honda Y, Watanabe N. Suppression of IgE antibody production after exposure to ozone in mice. Int Arch Allergy Appl Immunol. 1985;76(1):16–19. [PubMed]
  • Fujimaki H, Shiraishi F, Ashikawa T, Murakami M. Changes in delayed hypersensitivity reaction in mice exposed to O3. Environ Res. 1987 Jun;43(1):186–190. [PubMed]
  • Goldstein E, Bartlema HC, van der Ploeg M, van Duijn P, van der Stap JG, Lippert W. Effect of ozone on lysosomal enzymes of alveolar macrophages engaged in phagocytosis and killing of inhaled Staphylococcus aureus. J Infect Dis. 1978 Sep;138(3):299–311. [PubMed]
  • Gilmour MI, Park P, Selgrade MK. Ozone-enhanced pulmonary infection with Streptococcus zooepidemicus in mice. The role of alveolar macrophage function and capsular virulence factors. Am Rev Respir Dis. 1993 Mar;147(3):753–760. [PubMed]
  • Christman CA, Schwartz LW. Enhanced phagocytosis by alveolar macrophages induced by short-term ozone insult. Environ Res. 1982 Aug;28(2):241–250. [PubMed]
  • Driscoll KE, Vollmuth TA, Schlesinger RB. Acute and subchronic ozone inhalation in the rabbit: response of alveolar macrophages. J Toxicol Environ Health. 1987;21(1-2):27–43. [PubMed]
  • Oosting RS, van Golde LM, Verhoef J, Van Bree L. Species differences in impairment and recovery of alveolar macrophage functions following single and repeated ozone exposures. Toxicol Appl Pharmacol. 1991 Aug;110(1):170–178. [PubMed]
  • Devlin RB, McDonnell WF, Mann R, Becker S, House DE, Schreinemachers D, Koren HS. Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung. Am J Respir Cell Mol Biol. 1991 Jan;4(1):72–81. [PubMed]
  • Peterson ML, Harder S, Rummo N, House D. Effect of ozone on leukocyte function in exposed human subjects. Environ Res. 1978 Jun;15(3):485–493. [PubMed]
  • Goldstein E, Jordan GW, MacKenzie MR, Osebold JW. Methods for evaluating the toxicological effects of gaseous and particulate contaminants on pulmonary microbial defense systems. Annu Rev Pharmacol Toxicol. 1976;16:447–463. [PubMed]
  • Gardner DE. Use of experimental airborne infections for monitoring altered host defenses. Environ Health Perspect. 1982 Feb;43:99–107. [PMC free article] [PubMed]
  • MILLER S, EHRLICH R. Susceptibility to respiratory infections of animals exposed to ozone. I. Susceptibility to Klebsiella pneumoniae. J Infect Dis. 1958 Sep-Oct;103(2):145–149. [PubMed]
  • Ehrlich R, Findlay JC, Gardner DE. Effects of repeated exposures to peak concentrations of nitrogen dioxide and ozone on resistance to streptococcal pneumonia. J Toxicol Environ Health. 1979 Jul;5(4):631–642. [PubMed]
  • Ehrlich R, Findlay JC, Fenters JD, Gardner DE. Health effects of short-term inhalation of nitrogen dioxide and ozone mixtures. Environ Res. 1977 Oct;14(2):223–231. [PubMed]
  • Graham JA, Gardner DE, Blommer EJ, House DE, Ménache MG, Miller FJ. Influence of exposure patterns of nitrogen dioxide and modifications by ozone on susceptibility to bacterial infectious disease in mice. J Toxicol Environ Health. 1987;21(1-2):113–125. [PubMed]
  • Goldstein E, Lippert W, Warshauer D. Pulmonary alveolar macrophage. Defender against bacterial infection of the lung. J Clin Invest. 1974 Sep;54(3):519–528. [PMC free article] [PubMed]
  • Goldstein E, Tyler WS, Hoeprich PD, Eagle C. Ozone and the antibacterial defense mechanisms of the murine lung. Arch Intern Med. 1971 Jun;127(6):1099–1102. [PubMed]
  • Warshauer D, Goldstein E, Hoeprich PD, Lippert W. Effect of vitamin E and ozone on the pulmonary antibacterial defense mechanisms. J Lab Clin Med. 1974 Feb;83(2):228–240. [PubMed]
  • Gilmour MI, Park P, Doerfler D, Selgrade MK. Factors that influence the suppression of pulmonary antibacterial defenses in mice exposed to ozone. Exp Lung Res. 1993 May-Jun;19(3):299–314. [PubMed]
  • Thienes CH, Skillen RG, Hoyt A, Bogen E. Effects of ozone on experimental tuberculosis and on natural pulmonary infections in mice. Am Ind Hyg Assoc J. 1965 May-Jun;26(3):255–260. [PubMed]
  • Thomas GB, Fenters JD, Ehrlich R, Gardner DE. Effects of exposure to ozone on susceptibility to experimental tuberculosis. Toxicol Lett. 1981 Sep;9(1):11–17. [PubMed]
  • Fairchild GA. Effects of ozone and sulfur dioxide on virus growth in mice. Arch Environ Health. 1977 Jan-Feb;32(1):28–33. [PubMed]
  • Selgrade MK, Illing JW, Starnes DM, Stead AG, Ménache MG, Stevens MA. Evaluation of effects of ozone exposure on influenza infection in mice using several indicators of susceptibility. Fundam Appl Toxicol. 1988 Jul;11(1):169–180. [PubMed]
  • Wolcott JA, Zee YC, Osebold JW. Exposure to ozone reduces influenza disease severity and alters distribution of influenza viral antigens in murine lungs. Appl Environ Microbiol. 1982 Sep;44(3):723–731. [PMC free article] [PubMed]
  • BUELL GC, TOKIWA Y, MUELLER PK. POTENTIAL CROSSLINKING AGENTS IN LUNG TISSUE. FORMATION AND ISOLATION AFTER IN VIVO EXPOSURE IN OZONE. Arch Environ Health. 1965 Feb;10:213–219. [PubMed]
  • SCHEEL LD, DOBROGORSKI OJ, MOUNTAIN JT, SVIRBELY JL, STOKINGER HE. Physiologic, biochemical, immunologic and pathologic changes following ozone exposure. J Appl Physiol. 1959 Jan;14(1):67–80. [PubMed]
  • STOKINGER HE, SCHEEL LD. Ozone toxicity. Immunochemical and tolerance-producing aspects. Arch Environ Health. 1962 Mar;4:327–334. [PubMed]
  • Atwal OS, Samagh BS, Bhatnagar MK. A possible autoimmune parathyroiditis following ozone inhalation. II. A histopathologic, ultrastructural, and immunofluorescent study. Am J Pathol. 1975 Jul;80(1):53–68. [PubMed]
  • Wenzel DG, Morgan DL. In vitro inhibition of alveolar macrophage phagocytosis by ozone: absence of a role for serum or mode of ozone administration. Toxicol Lett. 1983 Aug;18(1-2):57–61. [PubMed]
  • Becker S, Madden MC, Newman SL, Devlin RB, Koren HS. Modulation of human alveolar macrophage properties by ozone exposure in vitro. Toxicol Appl Pharmacol. 1991 Sep 15;110(3):403–415. [PubMed]
  • Becker S, Jordan RL, Orlando GS, Koren HS. In vitro ozone exposure inhibits mitogen-induced lymphocyte proliferation and IL-2 production. J Toxicol Environ Health. 1989;26(4):469–483. [PubMed]
  • Becker S, Quay J, Koren HS. Effect of ozone on immunoglobulin production by human B cells in vitro. J Toxicol Environ Health. 1991 Nov;34(3):353–366. [PubMed]
  • Gilmour MI, Hmieleski RR, Stafford EA, Jakab GJ. Suppression and recovery of the alveolar macrophage phagocytic system during continuous exposure to 0.5 ppm ozone. Exp Lung Res. 1991 May-Jun;17(3):547–558. [PubMed]
  • Sanders VM, Fuchs BA, Pruett SB, Kerkvliet NI, Kaminski NE. Symposium on indirect mechanisms of immune modulation. Fundam Appl Toxicol. 1991 Nov;17(4):641–650. [PubMed]
  • Kleeberger SR, Kolbe J, Adkinson NF, Jr, Peters SP, Spannhake EW. The role of mediators in the response of the canine peripheral lung to 1 ppm ozone. Am Rev Respir Dis. 1988 Feb;137(2):321–325. [PubMed]
  • Schlesinger RB, Driscoll KE, Gunnison AF, Zelikoff JT. Pulmonary arachidonic acid metabolism following acute exposures to ozone and nitrogen dioxide. J Toxicol Environ Health. 1990 Dec;31(4):275–290. [PubMed]
  • Miller PD, Ainsworth D, Lam HF, Amdur MO. Indomethacin and cromolyn sodium alter ozone-induced changes in lung function and plasma eicosanoid concentrations in guinea pigs. Toxicol Appl Pharmacol. 1988 Apr;93(2):175–186. [PubMed]
  • Schelegle ES, Adams WC, Giri SN, Siefkin AD. Acute ozone exposure increases plasma prostaglandin F2 alpha in ozone-sensitive human subjects. Am Rev Respir Dis. 1989 Jul;140(1):211–216. [PubMed]
  • Sweet C, Smith H. Pathogenicity of influenza virus. Microbiol Rev. 1980 Jun;44(2):303–330. [PMC free article] [PubMed]
  • Sullivan JL, Mayner RE, Barry DW, Ennis FA. Influenza virus infection in nude mice. J Infect Dis. 1976 Jan;133(1):91–94. [PubMed]
  • Wells MA, Albrecht P, Ennis FA. Recovery from a viral respiratory infection. I. Influenza pneumonia in normal and T-deficient mice. J Immunol. 1981 Mar;126(3):1036–1041. [PubMed]
  • Wyde PR, Cate TR. Cellular changes in lungs of mice infected with influenza virus: characterization of the cytotoxic responses. Infect Immun. 1978 Nov;22(2):423–429. [PMC free article] [PubMed]
  • Wyde PR, Peavy DL, Cate TR. Morphological and cytochemical characterization of cells infiltrating mouse lungs after influenza infection. Infect Immun. 1978 Jul;21(1):140–146. [PMC free article] [PubMed]
  • Wyde PR, Couch RB, Mackler BF, Cate TR, Levy BM. Effects of low- and high-passage influenza virus infection in normal and nude mice. Infect Immun. 1977 Jan;15(1):221–229. [PMC free article] [PubMed]
  • Berlin BS, Cochran KW. Delay of fatal pneumonia in x-irradiated mice inoculated with mouse-adapted influenza virus, PR8 strain. Radiat Res. 1967 Jun;31(2):343–351. [PubMed]
  • Singer SH, Noguchi P, Kirschstein RL. Respiratory diseases in cyclophosphamide-treated mice. II. Decreased virulence of PR8 influenza virus. Infect Immun. 1972 Jun;5(6):957–960. [PMC free article] [PubMed]
  • Suzuki F, Oya J, Ishida N. Effect of antilymphocyte serum on influenza virus infection in mice. Proc Soc Exp Biol Med. 1974 May;146(1):78–84. [PubMed]
  • Cate TR, Mold NG. Increased influenza pneumonia mortality of mice adoptively immunized with node and spleen cells sensitized by inactivated but not live virus. Infect Immun. 1975 May;11(5):908–914. [PMC free article] [PubMed]
  • Jakab GJ, Hmieleski RR. Reduction of influenza virus pathogenesis by exposure to 0.5 ppm ozone. J Toxicol Environ Health. 1988;23(4):455–472. [PubMed]
  • Jakab GJ, Bassett DJ. Influenza virus infection, ozone exposure, and fibrogenesis. Am Rev Respir Dis. 1990 May;141(5 Pt 1):1307–1315. [PubMed]
  • Nayak DP, Kelley GW, Underdahl NR. The effect of varied inoculums on the distribution and progression of Influenza virus (S-15) in lungs of mice. Am J Vet Res. 1965 Jul;26(113):984–990. [PubMed]
  • Jakab GJ. Suppression of pulmonary antibacterial activity following Sendai virus infection in mice: dependence on virus dose. Arch Virol. 1975;48(4):385–390. [PubMed]
  • Jakab GJ, Warr GA. Lung defenses against viral and bacterial challenges during immunosuppression with cyclophosphamide in mice. Am Rev Respir Dis. 1981 May;123(5):524–528. [PubMed]
  • Blandford G. Studies on the immune response and pathogenesis of Sendai virus infection of mice. III. The effects of cyclophosphamide. Immunology. 1975 May;28(5):871–883. [PubMed]
  • Tashiro M, Tobita K, Seto JT, Rott R. Comparison of protective effects of serum antibody on respiratory and systemic infection of Sendai virus in mice. Arch Virol. 1989;107(1-2):85–96. [PubMed]
  • Parker JC, Whiteman MD, Richter CB. Susceptibility of inbred and outbred mouse strains to Sendai virus and prevalence of infection in laboratory rodents. Infect Immun. 1978 Jan;19(1):123–130. [PMC free article] [PubMed]
  • Warr GA, Jakab GJ, Hearst JE. Alterations in lung macrophage immune receptor(s) activity associated with viral pneumonia. J Reticuloendothel Soc. 1979 Oct;26(4):357–366. [PubMed]
  • Jakab GJ, Warr GA, Sannes PL. Alveolar macrophage ingestion and phagosome-lysosome fusion defect associated with virus pneumonia. Infect Immun. 1980 Mar;27(3):960–968. [PMC free article] [PubMed]
  • Garlinghouse LE, Jr, Van Hoosier GL., Jr Studies on adjuvant-induced arthritis, tumor transplantability, and serologic response to bovine serum albumin in Sendai virus-infected rats. Am J Vet Res. 1978 Feb;39(2):297–300. [PubMed]
  • Anderson MJ. Innate cytotoxicity of CBA mouse spleen cells to Sendai virus-infected L cells. Infect Immun. 1978 Jun;20(3):608–612. [PMC free article] [PubMed]
  • Kay MM. Long term subclinical effects of parainfluenza (SENDAI) infection on immune cells of aging mice. Proc Soc Exp Biol Med. 1978 Jul;158(3):326–331. [PubMed]
  • Stobo JD, Paul WE. Functional heterogeneity of murine lymphoid cells. 3. Differential responsiveness of T cells to phytohemagglutinin and concanavalin A as a probe for T cell subsets. J Immunol. 1973 Feb;110(2):362–375. [PubMed]
  • Luster MI, Munson AE, Thomas PT, Holsapple MP, Fenters JD, White KL, Jr, Lauer LD, Germolec DR, Rosenthal GJ, Dean JH. Development of a testing battery to assess chemical-induced immunotoxicity: National Toxicology Program's guidelines for immunotoxicity evaluation in mice. Fundam Appl Toxicol. 1988 Jan;10(1):2–19. [PubMed]
  • Luster MI, Portier C, Pait DG, White KL, Jr, Gennings C, Munson AE, Rosenthal GJ. Risk assessment in immunotoxicology. I. Sensitivity and predictability of immune tests. Fundam Appl Toxicol. 1992 Feb;18(2):200–210. [PubMed]
  • Gunnison AF, Finkelstein I, Weideman P, Su WY, Sobo M, Schlesinger RB. Age-dependent effect of ozone on pulmonary eicosanoid metabolism in rabbits and rats. Fundam Appl Toxicol. 1990 Nov;15(4):779–790. [PubMed]
  • Gunnison AF, Weideman PA, Sobo M, Koenig KL, Chen LC. Age-dependence of responses to acute ozone exposure in rats. Fundam Appl Toxicol. 1992 Apr;18(3):360–369. [PubMed]
  • Elsayed NM, Mustafa MG, Postlethwait EM. Age-dependent pulmonary response of rats to ozone exposure. J Toxicol Environ Health. 1982 May-Jun;9(5-6):835–848. [PubMed]
  • Montgomery MR, Raska-Emery P, Balis JU. Age-related difference in pulmonary response to ozone. Biochim Biophys Acta. 1987 Feb 11;890(2):271–274. [PubMed]
  • Cavender FL, Singh B, Cockrell BY. The effects in rats and guinea pigs from six months exposures to sulfuric acid mist, ozone, and their combination. J Environ Pathol Toxicol. 1978 Nov-Dec;2(2):485–492. [PubMed]
  • Mustafa MG, Elsayed NM, Quinn CL, Postlethwait EM, Gardner DE, Graham JA. Comparison of pulmonary biochemical effects of low-level ozone exposure on mice and rats. J Toxicol Environ Health. 1982 May-Jun;9(5-6):857–865. [PubMed]
  • Guth DJ, Warren DL, Last JA. Comparative sensitivity of measurements of lung damage made by bronchoalveolar lavage after short-term exposure of rats to ozone. Toxicology. 1986 Aug;40(2):131–143. [PubMed]
  • Hatch GE, Slade R, Stead AG, Graham JA. Species comparison of acute inhalation toxicity of ozone and phosgene. J Toxicol Environ Health. 1986;19(1):43–53. [PubMed]
  • Sagai M, Arakawa K, Ichinose T, Shimojo N. Biochemical effects on combined gases of nitrogen dioxide and ozone. I. Species differences of lipid peroxides and phospholipids in lungs. Toxicology. 1987 Nov;46(3):251–265. [PubMed]
  • Goldstein BD, Lai LY, Ross SR, Cuzzi-Spada R. Susceptibility of inbred mouse strains to ozone. Arch Environ Health. 1973 Dec;27(6):412–413. [PubMed]
  • Kleeberger SR, Bassett DJ, Jakab GJ, Levitt RC. A genetic model for evaluation of susceptibility to ozone-induced inflammation. Am J Physiol. 1990 Jun;258(6 Pt 1):L313–L320. [PubMed]
  • Kleeberger SR, Levitt RC, Zhang LY. Susceptibility to ozone-induced inflammation. II. Separate loci control responses to acute and subacute exposures. Am J Physiol. 1993 Jan;264(1 Pt 1):L21–L26. [PubMed]
  • Clark EA, Harmon RC. Genetic control of natural cytotoxicity and hybrid resistance. Adv Cancer Res. 1980;31:227–285. [PubMed]
  • Sasazuki T, Nishimura Y, Muto M, Ohta N. HLA-linked genes controlling immune response and disease susceptibility. Immunol Rev. 1983;70:51–75. [PubMed]
  • Skamene E. Genetic regulation of host resistance to bacterial infection. Rev Infect Dis. 1983 Sep-Oct;5 (Suppl 4):S823–S832. [PubMed]
  • Stewart GA, Holt PG. Immunogenicity and tolerogenicity of a major house dust mite allergen, Der p I from Dermatophagoides pteronyssinus, in mice and rats. Int Arch Allergy Appl Immunol. 1987;83(1):44–51. [PubMed]

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