Fibrosis is the production of excessive amounts of connective tissue, i.e., scar formation, in the course of reactive and reparative processes. Fibrosis develops as a consequence of various underlying diseases and presents a major diagnostically and therapeutically unsolved problem. In this review, we postulate that fibrosis is always a sequela of inflammatory processes and that the many different causes of fibrosis all channel into the same final stereotypical pathways. During the inflammatory phase, both innate and adaptive immune mechanisms are operative. This concept is exemplified by fibrotic diseases that develop as a consequence of tissue damage, primary inflammatory diseases, fibrotic alterations induced by foreign body implants, "spontaneous" fibrosis, and tumor-associated fibrotic changes.

The mechanism that may cause degenerative fibrotic skin lesions was studied in situ using skin biopsies from patients with systemic sclerosis (

As the aging population in developed countries is growing in both numbers and percentage, the medical, social, and economic burdens posed by nonhealing wounds are increasing. Hence, it is all the more important to understand the mechanisms underlying age-related impairments in wound healing. The purpose of this article is to give a concise overview of (1) normal wound healing, (2) alterations in aging skin that have an impact on wound repair, (3) alterations in the repair process of aged skin, and (4) general factors associated with old age that might impair wound healing, with a focus on the literature of the last 10 years.

Fibrosis is an important health problem and its pathogenetic principles are still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases. However, irrespective of the primary cause, fibrotic tissue is always infiltrated by mononuclear immune cells. In most instances the reason for the attraction of these cells to fibrotic tissue and their proliferation remains to be determined, however their cytokine profile shows clear-cut proinflammatory and profibrotic characteristics. In this review we discuss the innate and adaptive immune reactions associated with the development of fibrosis and the molecular basis of the profibrotic mechanisms taking place in systemic sclerosis (scleroderma), arteriosclerosis and peri-silicone mammary implant fibrosis. Fibrosis: a disease with an immune-mediated etiologyFibrosis, i.e. excessive extracellular matrix (ECM) formation with proliferation and activation of myofibroblasts, is a major global health problem, but its etiology, pathogenesis, diagnosis and therapy have yet to be addressed in detail in either basic or clinical research settings. In principle, fibrosis can occur as a consequence of many different pathologic conditions (Figure 1), the most important of which arise either spontaneously, from tissue damage, inflammatory disease, in response to foreign implants, or from tumors (see Table 1).Although the pathologic processes initiating and perpetuating these processes are rather diverse, from a biochemical and pathohistological view the end stage of the development of fibrosis seems to be very stereotypic. Thus, in all cases studied the early stages of fibrotic conditions are characterized by immunologic-inflammatory hallmarks, viz. a perivascular infiltration by mononuclear cells and the subsequent imbalance of anti-and profibrotic cytokine profiles. In most of these instances, the original antigenic stimuli triggering the lymphoid infiltration have not been identified. The emphasis of this review is placed on the general role of innate and adaptive immunity, and the respective cytokines involved in the development of fibrosis.