Many activities are now ascribed to the monokine interleukin 1 including enhancement of immune responses, stimulation of thymocyte proliferation, activation of B cells, stimulation of proteinase and prostaglandin production by connective tissue cells, stimulation of the production of acute phase proteins, induction of fever and the induction of neutrophilia. These activities were thought to be due to various different factors, but are now considered probably due to very similar, if not identical, molecules. The term interleukin 1 (IL-1) was coined to describe the factor released by monocyte/macrophages which acts on T and B lymphocytes. Only after this definition had been accepted was it shown that target cells other than lymphocytes were affected by IL-1. Products of human blood monocytes (mononuclear cell factor, MCF) have been implicated in the pathogenesis of inflammatory diseases such as rheumatoid arthritis and periodontal disease. Bone resorption is often a feature of such diseases, and monocytes are frequently found at sites of localized bone resorption. Preliminary experiments with monocyte-conditioned medium indicated that MCF could stimulate bone resorption. We therefore undertook this study to verify these observations and to determine whether purified IL-1 could stimulate connective tissue breakdown in vitro.
Interleukin-1 (IL-1) is a macrophage derived mediator whose properties suggest that it could play a role in the pathology of arthritis. To test this hypothesis, joint fluids from patients with several different arthritides were tested. Small amounts of IL-1-like activity were recovered from many of these joint fluids after affinity chromatography over a column of rabbit antihuman IL-1. Positive fluids were obtained from patients with rheumatoid arthritis, psoriatic arthritis, Reiter's syndrome, osteoarthritis, gout, and traumatic arthritis.Upon gel filtration, the joint derived factor displayed a molecular weight distribution similar to that of IL-1 derived from human monocytes stimulated in vitro. These results suggest that IL-1 is present in joint effusions and, therefore, might contribute to joint destruction.Interleukin-1 (IL-1) is a 12,000-18,000 dalton protein secreted by stimulated monocyte-macrophages, which has a number of important biologic activities. These include lymphocyte activation, the stimulation of hepatic acute phase protein production, the induction of neutrophilia, and pyrogenicity (1). Furthermore, a mononuclear cell factor probably iden-
The process of induction of bone formation, which follows bone resorption during normal and pathological bone turnover, is well documented. However, the mechanisms responsible for this process are unclear. Mononuclear phagocytes present at the sites of bone remodeling could play a role in this "coupling" of bone formation to bone resorption. This study was designed to investigate such a possibility. By measuring both the increase in [3Hjthymidine incorporation and in cell number, we found that human monocytes in culture released factors capable of stimulating the proliferation of osteoblast-like cells derived from human bone. Rapidly dividing cells exhibited a greater response to interleukin 1 (IL-1) than confluent cells.The factors are similar to IL-1 in that they exhibited the same molecular weight and isoelectric point, were present in fractions that contained IL-1 activity after gel filtration chromatography and isoelectric focusing, and showed similar doseresponse characteristics. Proliferation was more marked when prostaglandin production by the cells, which was also stimulated by these factors, was inhibited by indomethacin.A factor produced by monocytes that affects osteoblast activity may be important in the coupling of osteoclast and osteoblast actions.
Should a highly pathogenic avian influenza virus, such as the H5N1 virus type currently circulating in birds, become transmissible among humans, an effective vaccine, rapidly available in vast quantities, would be the best tool to prevent high case-fatalities and the breakdown of health and social services. The number of vaccine doses that could be produced on demand has risen sharply over the last few years; however, it is still alarmingly short of the 13 billion doses that would be needed if two doses were required to protect fully the world's population. Most developing countries would be last in the queue to benefit from a pandemic vaccine. The World Health Organization, together with governments, the pharmaceutical industry and other stakeholders, has been implementing the global pandemic influenza action plan to increase vaccine supply since 2006. Building capacity in developing countries to manufacture influenza vaccine is an integral part of this plan, as well as research and development into more efficacious technologies, e.g. those that allow significant dose-sparing. To this end, the influenza vaccine technology transfer initiative was launched in 2007 and, to date, vaccine manufacturers in 11 developing countries have received grants to acquire the capacity to produce inactivated or live attenuated influenza vaccine for their populations. In addition, a centralized 'hub' has been established to facilitate training in the new technologies for scientists and regulators in the countries. This supplement of Vaccine is devoted to showcasing the interim results of the WHO initiative and the impressive progress made by the developing country manufacturers.
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