Anti-interleukin-10 antibody restores burn-induced defects in T-cell function

• Published in: Surgery Vol. 122; no. 2; pp. 146 - 152
• Main Authors: Kelly, John L, Lyons, Ann, Soberg, Christopher C, Mannick, John A, Lederer, James A
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01-08-1997
• Subjects: AIDS/HIV; Animals; Antibodies, Monoclonal - pharmacology; Antibody Formation; Burns - immunology; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Freund's Adjuvant; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunoglobulin G - pharmacology; Immunoglobulin Isotypes - blood; Interferon-gamma - biosynthesis; Interleukin-10 - immunology; Interleukin-10 - physiology; Interleukin-2 - biosynthesis; Lymph Nodes - immunology; Lymphocyte Activation; Male; Mice; Mice, Inbred A; Ovalbumin - immunology; Rats; Reference Values; Spleen - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Th1 Cells - immunology; Th2 Cells - immunology; Trinitrobenzenesulfonic Acid - immunology
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/S0039-6060(97)90003-9

Background. Studies have shown that susceptibility to sepsis after severe injury correlated with reduced production of T-helper 1 (Th1) cytokines (interleukin-2 [IL-2] and interferon-γ [IFN-γ]) and a persistence of T-helper 2 (Th2) cytokines (IL-4 and IL-10). The mechanisms responsible for this effect are not clear. We used a T-dependent antigen to study both the effect of burn injury on antigen-specific Th functions in vivo and the effect of anti-IL-10 antibody on these functions.
Methods. Male A/J mice were anesthetized and given a 25% scald burn or a sham burn. On day 0 all mice were immunized with 100 μg trinitrobenzene sulfonic acid (TNP) haptenated ovalbumin (TNP-OVA) in complete Freund's adjuvant. Mice (10 per group) were given 250 μg monoclonal rat antimurine IL-10 antibody (anti-IL-10 MAB) or control rat immunoglobin G (IgG) on day 0 and 100 μg anti-IL-10 MAB or IgG on day 2. On day 10 the mice were killed to obtain serum and spleen cells. TNP-specific serum antibody isotype titers were determined by enzyme-linked immunosorbent assay (ELISA). Splenocyte proliferation and cytokine production in response to TNP-OVA or to anti-CD3 MAB were determined by tritiated thymidine incorporation and by ELISA, respectively.
Results. Burn injury resulted in depressed levels of the TNP-specific IgG2a antibody isotype (Th1 dependent), whereas TNP-specific IgG1 and IgE (Th2 dependent) levels were not decreased in burn versus sham burn mice. Anti-IL-10 MAB but not IgG restored the IgG2a response. Burn injury also resulted in reduced TNP-OVA-specific proliferation of splenocytes, whereas anti-CD3 proliferation was equivalent in burn and sham mice. TNP-OVA-specific IL-2 and IFN-γ production were significantly reduced by burn injury. Anti-IL-10 MAB restored TNP-OVA-specific proliferation and antigen-specific IL-2 and interferon-γ production by splenocytes from burn mice.
Conclusions. Burn injury induces the loss of antigen-specific Th1 cell function, and IL-10 acts as a trigger to down-regulate Th1 activity after injury.