Decreased production of and response to interleukin-2 by cultured lymphocytes from patients with systemic lupus erythematosus.

Objective. Both antibody and cell-mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell-mediated responses have not yet been assessed. This study was therefore undertaken to assess cell-mediated responses to influenza vaccination in patients with SLE.Methods. Fifty-four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cellmediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon-␥ (IFN␥) enzymelinked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test.Results. Prior to vaccination, patients with SLE had fewer IFN␥ spot-forming cells against A/H1N1 compared with control subjects and a lower frequency of IFN␥-positive CD8؉ T cells. After vaccination, the number of IFN␥ spot-forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4؉ T cells producing tumor necrosis factor and interleukin-2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8؉ T cell response. For A/H3N2-specific responses, results were comparable. Diminished cell-mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1-specific and A/H3N2-specific antibody titers after vaccination was lower in patients compared with control subjects.Conclusion. In addition to a decreased antibody response, cell-mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections.

Section: Discussionmentioning

confidence: 78%

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Holvast¹,

Assen²,

Haan³

et al. 2009

“…Both factors greatly accentuate NK cell activity and may be necessary for normal NK cell function (15). Significantly, production of these factors is often impaired in SLE (17,18). However, impaired production of these lymphokines in SLE does not appear to be directly related to dysfunction of the NK cell (19)(20)(21).…”

mentioning

confidence: 99%

Relationship between circulating interferon and anti‐interferon antibodies and impaired natural killer cell activity in systemic lupus erythematosus

Sibbitt

Gibbs

Kenny

et al. 1985

Interferon (IFN) production and response are impaired in a high percentage of systemic lupus erythematosus (SLE) patients. In addition, elevated serum levels of a-IFN or anti-a-IFN antibodies are present in some SLE patients. This study examined the relationship of circulating IFN and anti-IFN antibodies to the impairment of natural killer (NK) cell function in SLE. All 15 SLE patients studied had measurable circulating a-IFN, while the normal controls had minimal serum IFN. Neither patient nor control sera contained any detectable anti-a-IFN activity. However, most of the SLE patients demonstrated defects in NK cell function. Because these defects in NK cell function appeared to be associated with circulating IFN, but not anti-IFN, antibodies, the effect of prolonged in vitro IFN exposure on NK cell function of peripheral blood qpnonuclear cells was determined. It was found that prolonged exposure to IFN induced both an apparent defect in IFN response and a definite impairment of baseline NK cell function. These results suggest that prolonged elevation of circulating a-IFN levels could be responsible, in part, for the defects in natural cytotoxicity present in SLE.Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by multiFrom

“…This is also of interest in consideration of the relatively low natural killer cell activity observed in SLE and rheumatoid arthritis (13,14). An additional feature common to human and murine SLE is low production of interleukin-2 (IL-2) (15,16). Preliminary in vitro experiments indicate that treatment with LS-2616 enhances IL-2 production in rats (Maksimova et al: in preparation).…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of autoimmunity in mrl/1 mice with ls‐2616, a new immunomodulator

Tarkowski¹,

Gunnarsson²,

Nilsson³

et al. 1986

Autoimmune MRLlI mice were treated with a recently developed substance with immunomodulating properties, LS-2616. Treatment was initiated at the age of 8 weeks, before the onset of clinically apparent disease, and at 16 weeks of age, after development of established lupus disease. Beneficial therapeutic effects were obtained, even when LS-2616 was administered at the lowest dose tested (1 mglmouselweek) to 16-week-old mice. The effects of LS-2616 on longevity, as well as on development of lymphadenopathy, splenomegaly, glomerulonephritis, and vasculitis, were pronounced and were comparable with those of cyclophosphamide. The results obtained suggest a potential role for LS-2616 in the treatment of autoimmune disease in humans.MRL-lprllpr (MRLl1) mice spontaneously develop a severe autoimmune disease which is characterized by massive generalized lymphadenopathy, arthritis, arteritis, and immune complex-mediated glomerulonephritis. Serologic abnormalities comprise hypergammaglobulinemia, occurrence of antibodies against native DNA, rheumatoid factor, and circulating immune complexes. The MRL/l strain may thus be regarded as a model for human systemic lupus erythematosus (SLE) and rheumatoid arthritis (1,2). Studies of MRL/I mice and other murine models of SLE, e.g., the New Zealand blacklNew Zealand white mouse model, have significantly contributed to our understanding of immunologic mechanisms also relevant to human autoimmunity. Furthermore, the above-mentioned autoimmune mouse strains have been used to document possible therapeutic effects of new compounds (3,4).We describe here the effects of a newly synthesized, immunomodulating chemical compound, LS-2616 (5). Treatment of MRLll mice with LS-2616 was initiated at different stages of disease, and its effects on survival, development, and severity of glomerulonephritis, vasculitis, and lymphadenopathy were studied. The effects of LS-2616 were compared with those of cyclophosphamide, a pharmacologic compound with well-documented cytotoxic properties. MATERIALS AND METHODSMice. MRLl1 mice, purchased from Jackson Laboratories (Bar Harbor, ME), were bred and maintained in the animal facilities of the Department of Medical Microbiology, University of Goteborg. Animals were randomly selected, virgin MRLll females.Procedures. Proteinuria was determined by means of Albustix (Ames, Elkhart, IN). Serum levels of antibodies against native DNA were measured by the indirect immunofluorescence method using Crithidiu luciliue as substrate (6). Serum levels of IgG were measured by radial immunodiffusion technique (7).