INFLAMMATION-INDUCED CHANGES IN THE PHENOTYPE AND CYTOKINE PROFILE OFCELLS MIGRATING THROUGH SKIN AND AFFERENT LYMPH

In the present study, we have localized cytokine-secreting cells withi n an ectoparasite-induced inflammatory lesion and monitored the phenot ype and cytokine profile of cells migrating from the inflammatory lesi on to the local draining lymph node via the afferent lymphatics. Inter leukin (IL)-8-producing cells were first detected in skin within 6 hr of infection, with increased numbers observed at 24 and 48 hr post inf ection. While these cells were concentrated within the neutrophil infl ux, adjacent to disrupted epidermis; they were also found scattered th roughout the surrounding dermis in areas where significant cellular in filtration was not apparent. IL-1 alpha- and IL-1 beta-producing cells could not be detected until 24 hr after infection and were restricted to areas of intense neutrophil accumulation. Concurrent with the onse t of inflammation was a threefold increase in the total number of cell s migrating through the draining afferent lymph. This increase in cell ularity was due primarily to increased migration of CD4 and gamma delt a T cells. Cytokine mRNA synthesis by migrating afferent lymph cells w as examined by reverse transcription-polymerase chain reaction (RT-PCR ) analysis of RNA extracted prior to, and at regular intervals during the course of the inflammatory response. IL-1 beta and IL-8, but not I L-1 alpha or IL-6 mRNA, was detected in migrating afferent lymph cells . Tumour necrosis factor (TNF)-alpha-specific mRNA was present in migr ating afferent lymph cells at all time points both prior to, and follo wing infection. Soluble IL-8 protein, but not IL-1 alpha, IL-1 beta or TNF-alpha protein, could be detected in lymph, with the amount of IL- 8 detected increasing as the infection progressed. mRNA coding for cyt okines associated with T-cell activation, such as IL-2, IL-4 or interf eron (IFN)-gamma, was also detected in migrating cells, although the c ytokine profiles of different experimental animals were extremely vari able.