Preface

Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory arthritis, which features destruction of synovial joints, systemic inflammation, functional disability, reduced quality of life, and increased morbidity and mortality. It is relatively common, having a world-wide prevalence of between 0.5-2%, and is associated with huge social and economic costs. Consequently, it is the most important of the inflammatory arthritides.

The aim of *Rheumatoid Arthritis – Etiology, Consequences and Co-Morbidities* is not to provide a comprehensive commentary on RA (several of these are already in publication), but rather to provide interesting, thought-provoking, and up-to-date perspectives on a variety of aspects of current research into this condition. In taking this approach, *Rheumatoid Arthritis – Etiology, Consequences and Co-Morbidities* includes topics not usually covered by conventional publications. As such, it is an ideal reference and source of inspiration and direction for investigators, whatever their level, in the challenging and exciting field of rheumatology research.

This book is broadly divided into: "Etiology" (chapters 1-10), and "Consequences and Co-Morbidities" (chapters 11-16).

The editor would like to thank the chapter authors for their excellent contributions, and extend to them the wish that their current and future research endeavors are fruitful. Special thanks are also given to Anja Filipovic and other InTech staff for their expert editorial assistance in publishing this book.

RA is an exciting condition to investigate. Hopefully, this book will help to advance research into the mechanisms and treatment of the disease.

> **Dr. Andrew B. Lemmey**  School of Sport, Health & Exercise Sciences, College of Health & Behavioral Sciences, Bangor University, UK

**Part 1** 

**Etiology** 

**Part 1** 

**Etiology** 

**1** 

Takashi Usui

*Japan* 

**Cytokine Profile of T Cells in the Joints** 

*Center for Innovation in Immunoregulative Technology and Therapeutics,* 

*Graduate School of Medicine, Kyoto University* 

**of Rheumatoid Arthritis and Its Murine Models** 

Rheumatoid arthritis (RA) is a chronic autoimmune disease that results in the destruction of cartilage and bone in joints. The murine Collagen-Induced Arthritis (CIA) model has been used to investigate the pathogenesis of RA representatively, because it shares many features with RA (Courtenay, et al., 1980; Luross & Williams, 2001). Susceptibility to arthritis of both CIA and RA is associated with the specific major histocompatibility complex class II allele (Gregersen, et al., 1987; Wooley, et al., 1989). In addition, autoantibodies to type II collagen (CII) have been detected from the synovial fluid of RA patients and it has an aggravating effect in both CIA mice and RA (Clague & Moore, 1984; Cook, et al., 1996; Mullazehi, et al., 2007; Tarkowski, et al., 1989). Finally, pathogenic contributions of CD4+ helper T (Th) cells have been reported in both CIA mice and RA (Weyand & Goronzy, 1999; Weyand, et al., 1998). More recently, the SKG mouse which carries a point mutation of the gene encoding zeta-chain-associated protein kinase 70 (ZAP-70) has been reported as a new model of RA. However, there is little information available about the similarities and differences in the

Interleukin-17 (IL-17) is a cytokine secreted by T cells, natural killer (NK) cells, and neutrophils (Ferretti, et al., 2003), and it induces IL-6, IL-8, chemokine, and metalloproteinase production by target cells (Weaver, et al., 2007). Central pathogenic roles of IL-17 in CIA have also been reported recently. For example, systemic or local IL-17 gene transfer aggravated CIA, whereas administration of an IL-17-blocking antibody ameliorated CIA even after the onset of arthritis (Lubberts, et al., 2001; Lubberts, et al., 2004) and IL-17 deficient mice also showed reduced severity of CIA (Nakae, et al., 2003). Furthermore, IL-23 deficient mice, which show impaired Th17 response, do not exhibit CIA because IL-23 is an essential factor for the maintenance of Th17 cells (Murphy, et al., 2003). Consequently, although the pathological contribution of IL-17

In the present study, we analyzed the phenotypes and cytokine profiles of T cells in the joints of CIA mice kinetically, for the first time, and then analyzed those of SKG mice and RA.

To analyze the phenotype and cytokine profile of T cells in the joints of CIA mice, we choose foot pad injection for CII-CFA (complete Freund's adjuvant) instead of tail base injection to

**2. Most of the IL-17-producing T cells in the swollen joints of CIA were** 

pathogenesis of arthritis among these murine models and RA.

to CIA is evident, it remains unclear with RA.

**gamma/delta T cells** 

**1. Introduction**
