Interferons and rheumatoid arthritis: insight into interferon biology?

Browning, Jeffrey L.

doi:10.1016/0167-5699(87)90212-x

Cited by 41 publications

(10 citation statements)

References 31 publications

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“…On day 45. the median number of arthritic limbs per mouse in the IFN-7-treatedgroupwas3-0(range2 4). This was significantly higher (/'<O-OI; Mann Whitney f^-test) than the number of arthritic limbs per mouse in the L2-3D9-treated group (median 1-5; range I 3) or the PBS-treated group (median 1-5; ratige [1][2][3]. No diflcrences were seen between the L2-3D9-treated group and the PBS-trcated group, indicating that hamster igGl did not modify disease outcome nonspecitically.…”

Section: Anti-ien-'i Treatment Before the Onset Of Arthritismentioning

confidence: 86%

Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma

Williams

Feldmann

et al. 1993

Clinical and Experimental Immunology

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SUMMARYWe have tested the effect of administering H22, a hamster neutralizing MoAb to murine interferongamma (IFN-'/) in collagen-induced arthritis. Mice were initTtuni7ed with human type II collagen in adjuvant on day 1 and boosted with soluble collagen on day 21. H22 was administered (250 ng. intraperitoneal!y)either during the induction of arthritis (on daysO, 6, 13 and 20) or around the time ofdiscasc manifestation (on days 21, 28, 35 and 42). Control mice received either an isotypc-matched non-neutralizing MoAb or saline. Both treatment regimes gave sitnilar results. Treattncnt with H22 did not signifieantly affect the incidence of arthritis, time ofonset, degree of oedetiia. histopathological severity, or tcvcl of anti-type II collagen IgG. However, a highly signiticanl increase (P<0'01) in the number of limbs affected by arthritis was observed in the H22-treated group, irrespective of whether the antibody was administered during the induction of arthritis, or during the time of clinical manifcstalion of disease. From these results it was concluded that anti-lFN-y treatment caused an inerease in the niitnber of arthritic lesions, but did not affect the severity of each individual lesion.Keywords interferon-gamma collagen-induced arthritis DBA/1 miee INTRODirCTION Much of the rcsearcb thai has been carried oul into the roles played by cytokines in chronic inflammatory conditions sueh as rheumatoid arthritis (RA) has focused on the identification of these tnolecules in affected tissues, and on the in vitro properties that they exhibit. It is itnportant to establish, however, which of these properties are important in vivo, since this information is critical for the development of therapeutic strategies based on the modulation of cytokine aetivity. For example, on the basis of in vitro studies, a wide range of both pro-and antiinllatnmatory properties have been described for interferongamma (1 FN-v) {1], but it is not known which of these properties is pathologically relevant. One potentially useful approach to the study ofthe pathological importance of eytokines in vivo is to adtninister cytokine-specilie neutralizing antibodies in particular disease situations. For example, the role of tumour necrosis factor in collagen-induced arthritis was established by adtninistering MoAbs specitic for this eytokine [2,3j, Collagen-induced arthritis demonstrates marked similarities to human RA with respect to both elinteal and histological findings [4] and can therefore be used to study the effects of adtninislcring cytokines or agents capable of neutralizing cytokines in vivo-For exatnple. two studies have recently been published on the effect on collagen-induced arthritis of adtTtinistering reeombinant IFN-"/ to collagen-immunized DBA/1 mice.Correspondence: Richard Williams. Kennedy Institute of Rheumatology. 6 Bute Gardens. London W6 7DW. UK.In the first of these studies, higher ineidenec. earlier onset and increased severity of arthritis were demonstrated in mice given footpad injections of recombinant IFN--/ [5]. ...

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Section: Anti-ien-'i Treatment Before the Onset Of Arthritismentioning

confidence: 86%

Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma

Williams

Feldmann

et al. 1993

Clinical and Experimental Immunology

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“…3, Table 2). IFN-x, which has immunoregulatory effects [28] and which produces systemic symptoms when administered to human beings [29], was also produced on stimulating immune PBMC with coxiella antigens (Table 1).…”

Section: Monocyte Stimulationmentioning

confidence: 99%

Variation in interferon-gamma responses to Coxiella burnetii antigens with lymphocytes from vaccinated or naturally infected subjects

Izzo

Marmion

1993

Clinical and Experimental Immunology

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SUMMARYPrevious work in our laboratory has shown that lymphocytes from persons vaccinated with a formalin-inactivated Phase I Q fever vaccine (Q-Vax CSL Ltd) show a mitogenic response to Coxiella burnetii antigens. The mitogenic response is the sum of that from various subsets of CD4+, T helper cells, CD8+ T cells and probably B cells. It does not distinguish between T helper cell responses leading to formation of interferon-gamma (IFN-y)-a cytokine responsible for clearing intracellular infection with C. burnetii organisms-and responses of other T cell subsets which may produce disease-enhancing cytokines. The present study analyses (i) the capacity of Q-Vax to induce T cell sensitization which leads to IFN-y responses on antigen stimulation, and (ii) the immunomodulatory, (down-regulatory) effects of the Phase I lipopolysaccharide (LPS) of the organism, which interacts with monocyte/macrophages to limit IL-2 production and production of IFN-7/ by sensitized T lymphocytes.

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“…The former mechanism may be respon sible for the relative high la expression in transplants (see fig. 3) and the latter offers an explanation for the decreased proliferation of B cells after LPS stimulation in subcutaneous transplants [37,38]. Furthermore, the abnor mal high amount of macrophages in replants reflects the altered expression and kinetics of GMCSF [for literature concerning cytokine function and expression, see reviews in 39 and 40], As a general summary it can be stated that our results from morphological (kinetics and mass) and histological (immunoarchitecture) investigations of splenic regeneration fit the data from other groups dealing with this field [for a review, see 34], But beyond this level, the regeneration of splenic tissue must be seen in the context of the dynamic properties of the immune system involving many interactions between the transplants and the target tissue.…”

Section: Discussionmentioning

confidence: 99%

Immunoarchitecture and Specific Functions of Splenic Autotransplants at Different Implantation Sites

Thalhamer¹,

Leitner²,

Kurz³

et al. 1992

Eur Surg Res

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The present study deals with the morphological and functional development of intraomentally and subcutaneously implanted splenic tissue. Spleens and splenic transplants from 138 Lewis rats were investigated with immunohistological, immunological and molecular biological methods at different times after operation (up to 200 days postoperatively). The analysis of the development revealed a nonsignificant reduction concerning the weight of subcutaneous replants and a nonsignificant decrease of the weight of female transplants of both groups at different phases after operation. The cell composition of cell suspensions from spleen and both transplant types showed a deficiency of T, B, MHC-L cells and a certain macrophage subset (ED-3⁺ cells) in transplants. In a quantitative immunohistological analysis of compartments (red pulp, periarteriolar lymphoid sheaths, marginal zone and follicles) the T cell reduction was related to the Tsupp/cyt cells and T cell receptor bearing cells in the periarteriolar lymphoid sheaths, whereas the density of T helper cells was normal. In addition, a different homing of K-light chain positive and leukocyte common antigen (B cell type)-positive B cells in follicles and marginal zone was detected. The amount of two macrophage subsets (ED-1⁺ and ED-2⁺ cells) was increased in the red pulp. Only minor differences in the immunoarchitecture of transplants at different implantation sites were measured. A functional analysis of spleen compared to both transplant groups elicited a B cell defect after LPS stimulation in subcutaneous transplants and a reduced allogeneic response of both transplant types but a normal proliferation of T cells after ConA stimulation and a correct IgM antibody response against sheep red blood cells. The in vivo mRNA expression and the expression kinetics of interferon-γ and granulocyte-macrophage colony-stimulating factor after antigen stimulation differed in both transplant groups with a remarkable permanent expression of both mediators in subcutaneous transplants. It can be summarized that the results clearly indicate a development of spleen-like immunoarchitecture of intraomental replants with subtle cellular, functional and molecular alterations. In contrast, despite a comparable development, some severe functional defects occurred in subcutaneous implants pointing out the important role of interactions between the regenerating splenic tissue and the target tissue on a functional and molecular level.

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Interferons and rheumatoid arthritis: insight into interferon biology?

Cited by 41 publications

References 31 publications

Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma

Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma

Variation in interferon-gamma responses to Coxiella burnetii antigens with lymphocytes from vaccinated or naturally infected subjects

Immunoarchitecture and Specific Functions of Splenic Autotransplants at Different Implantation Sites

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