title: Interleukin-4-deficient BALB/c mice develop an enhanced Th1-like response but control cardiac inflammation following Borrelia burgdorferi infection.
abstract: Interleukin-4 has been reported to critically modulate Borrelia burgdorferi infection and Lyme arthritis in experimental murine models. To determine the in vivo role of IL-4 in controlling Lyme carditis, we compared immunological responses and the severity of cardiac inflammation in wild-type BALB/c (IL-4 +/+) and IL-4 deficient BALB/c (IL-4 -/-) mice infected with B. burgdorferi by tick-bite. At day 15 and 30 post-infection IL-4 -/- mice produced significantly greater titers of spirochete-specific IgG2a than the wild-type IL-4 +/+ mice, which produced significantly more spirochete-specific IgG1. Following in vitro antigenic stimulation with B. burgdorferi antigen, splenocytes from infected IL-4 -/- and IL-4 +/+ mice displayed similar magnitudes of proliferative responses at day 15 and 30 post-infection. At day 30 antigen-stimulated splenocytes from infected IL-4 -/- mice, however, produced significantly more IFN-gamma than those derived from similarly infected IL-4 +/+ mice, suggesting that Th1-influenced responses predominated in IL-4 -/- mice. Moreover, inflamed hearts from IL-4 -/- mice displayed higher levels of IFN-gamma and TNF-alpha transcripts as compared to IL-4 +/+ mice. At both time points antigen-stimulated splenocytes from IL-4 +/+ and IL-4 -/- mice produced significant amounts of IL-10 but those from IL-4 +/+ mice produced either no or little IL-4. Histopathology demonstrated typical Lyme carditis in both IL-4 +/+ and IL-4 -/- mice at day 15 and day 30. Although Borrelia-infected IL-4 -/- mice developed a more severe carditis on day 30, the carditis resolved by day 50, as it did in IL4 +/+ mice. These results indicate that although IL-4 may help limit the severity of Lyme carditis, its absence does not preclude resolution of cardiac lesions.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington. Avenue, Boston, MA 02115, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: J
authors.initials: J
authors.lastname: Elizondo
authors.forename: G M
authors.initials: GM
authors.lastname: Monteforte
authors.forename: L M
authors.initials: LM
authors.lastname: Stamm
authors.forename: H
authors.initials: H
authors.lastname: Bluethmann
authors.forename: P
authors.initials: P
authors.lastname: Katavolos
authors.forename: S R
authors.initials: SR
authors.lastname: Telford
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology*; D008193:Lyme Disease / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma