Changes with Age in Macrophage Modulated Immunity

Albright, Julia

Abstract

This application is related to research topic No. 25, """"""""Vaccines and immune response."""""""" It is concerned with """"""""methods to improve the immune response in older persons"""""""" and """"""""studies designed to characterize age-related immune dysfunction."""""""" The proposal is focused on determining the qualitative and/or quantitative changes that occur in the profile of soluble cytokine receptors and selected, other substances produced by monocytes/macrophages (Mo/MP) as humans age. This is a new line of research for the PI who over the past two years has gained experience in working with human leukocytes and has conducted initial studies on soluble receptors of Mo/MP, some of which are described in this application. The Mo of aged humans are alleged to be in an activated state. Aged humans also display the shift that occurs toward a much higher proportion of memory/activated (CD44+) T cells. The interaction between these two types of cells by direct contact almost certainly leads to the observed major change in soluble products of Mo/MP of the elderly compared to young subjects. It is this change in the profile of soluble products that we propose to investigate including: IL-12,IL-1s RII, IL-1ra, TNFsRI, TNFsRII, IL-6sR, sCD14 and neopterin (the latter a marker of Mo/MP activation). In addition, we will gain initial insight as to the probable roles of memory, CD4+ T cells and endotoxins in inducing the activated state of Mo/MP. The data obtained from this investigation will provide a much better concept of the roles of the soluble factors in dysregulation of immune responses and in the frequent chronic inflammation that characterize elderly humans.