Cytokines in osteoarthritis: Mediators or markers of joint destruction?

doi:10.1016/S0049-0172(96)80036-9

Seminars in Arthritis and Rheumatism

Volume 25, Issue 4, February 1996, Pages 254-272

https://doi.org/10.1016/S0049-0172(96)80036-9 Get rights and content

Abstract

Objective:

The integrity of articular cartilage is maintained by the balance between cytokine-driven anabolic and catabolic processes. Unregulated or excess influences of these molecules are thought to play a part in the pathophysiology of many joint diseases. However, the role of cytokines in osteoarthritis (OA) is not well established. Our aims are twofold: firstly to consider the evidence for the contribution of cytokines to the pathophysiology of OA and secondly to evaluate their potential as markers of disease activity in OA.

Methods:

Cytokine homeostasis, the role of catabolic and anabolic cytokines in maintaining cartilage integrity, and the contribution of such cytokines to destructive processes in OA were examined. Consideration was given to the interrelationship between cartilage, bone, and synovium in OA; metabolites produced by such structures were compared with cytokines as indicators of disease activity.

Results:

The evidence reviewed suggests that interleukin-1 (IL-1) and the less potenttumor necrosis factorα (TNFα) are mediators of joint damage in OA. The cytokines interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) were implicted in both destructive and protective mechanisms, suggesting a dual role. Metabolites of the different components of the joint provided a better measure of disease activity than cytokines.

Conclusions:

Experimental evidence is emerging that catabolic cytokines are mediatorsof joint damage in OA, although their usefulness as markers of disease activity is limited because of the need to monitor a wide range of ligands and their inhibitors simultaneously. In contrast, metabolites released from cells within bone, synovium, and cartilage related to disease activity and provided prognostic information.

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Further, an 86-bp repeat polymorphism in the IL1-receptor antagonist gene has been associated with increased risk of osteoporotic fractures [16]. As mentioned earlier, increased IL-1 levels have been detected in synovial fluids from patients with both rheumatoid arthritis and OA [17,18]. Further, IL-1 is up-regulated in OA cartilage tissue and OA chondrocytes seem to express higher levels of IL-1 receptor type 1 [19,20].
Osteoarthritis (OA) can be regarded as a chronic, painful and degenerative disease that affects all tissues of a joint and one of the major endpoints being loss of articular cartilage. In most cases, OA is associated with a variable degree of synovial inflammation. A variety of different cell types including chondrocytes, synovial fibroblasts, adipocytes, osteoblasts and osteoclasts as well as stem and immune cells are involved in catabolic and inflammatory processes but also in attempts to counteract the cartilage loss. At the molecular level, these changes are regulated by a complex network of proteolytic enzymes, chemokines and cytokines (for review: [1]). Here, interleukin-1 signaling (IL-1) plays a central role and its effects on the different cell types involved in OA are discussed in this review with a special focus on the chondrocyte.
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Cytokines in osteoarthritis: Mediators or markers of joint destruction?

Abstract

Objective:

Methods:

Results:

Conclusions:

Clin Rheum Dis

Trends Endocrinol Metab

Exp Cell Res

Baillieres Clin Rheumatol

Lancet

Semin Arthritis Rheum

Lancet

Clin Immunol Immunopathol

Cytokine

Immunol Today

J Biol Chem

Cytokine

J Biol Chem

Immunol Today

Arch Biochem Biophys

J Biol Chem

Arch Biochem Biophys

Lancet

A pessimistic view of serologic markers for diagnosis and management of osteoarthritis, biochemical, immunological and clinicopathologic barriers

J Rheumatol

Cartilage failure in osteoarthritis: Relevance of normal structure and function: A review

Clin An at

Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis

Arthritis Rheum

Anti-cytokines in rheumatoid arthritis: A novel strategy for therapeutic intervention

Cytokines in context

J Cell Biol

Cytokines and growth factors

IFNβ2/ BSF2/IL-6 is the monocyte-derived HSF that regulates receptor-specific acute phase gene regulation in hepatocytes

Ann NY Acad Sci

IL-10 inhibits cytokine production by activated macrophages

J Immunol

Interleukin-10 inhibits Cyokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes

J Exp Med

IL-4 reciprocally regulates IL-1 and IL-1 receptor antagonist expression in human monocytes

J Immunol

Demonstration of neutralising autoantibodies against IL-1α in sera from patients with rheumatoid arthritis

J Immunol

Purification and characterisation of a novel soluble receptor for interleukin-1

J Exp Med

Identification of two types of tumour necrosis factor receptors on human cell lines by monoclonal antibodies

Insulin-like growth factor-1 can decrease degradation and promote synthesis of proteoglycan in cartilage exposed to Cytokines

Biochem J

Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips. 11. Correlation of morphology with metabolic data

J Bone Joint Surg

Biochemistry and metabolism of cartilage in osteoarthritis

Cytokines in Arthritis

Cytokines and the chronic inflammation of rheumatic disease. 1. The presence of interleukin-1 in synovial fluids

Clin Exp Immunol

Isolation of an interleukin-1-like factor from human joint effusions

Arthritis Rheum

Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL-1

Clin Exp Immunol

Synovial fluid concentration of five different Cytokines in rheumatic diseases

Ann Rheum Dis

Cytokine inter-relationships and their association with disease activity in arthritis

Br J Rheum

Interleukin-1α and β production by cells isolated from membrane around aseptically loose total joint replacements

Ann Rheum Dis

Interleukin-1 production by activated macrophages surrounding loosened orthopaedic implants: Potential role in osteolysis

Br J Rheumatol

The interleukin-1 receptor in normal and osteoarthritic human articular chondrocytes

Arthritis Rheum

IL-1 β at physiological concentration stimulates degradation of human articular cartilage

Bone and Mineral

Susceptibility of normal and arthritic human articular cartilage to degradative stimuli

Br J Rheum

Levels of synovial fluid interleukin-1 receptor antagonist in rheumatoid arthritis and other arthropathies: Potential contribution from synovial fluid neutrophils

Arthritis Rheum

Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis

Arthritis Rheum

Biologic effects of an interleukin-1 receptor antagonist protein on interleukin-1 stimulated cartilage erosion. and chondrocyte responsiveness

Arthritis Rheum

Prediction of progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy

IFNβ₂/ BSF₂/IL-6 is the monocyte-derived HSF that regulates receptor-specific acute phase gene regulation in hepatocytes