Inflammation-induced changes in the phenotype and cytokine profile of cells migrating through skin and afferent lymph

Abstract

In the present study, we have localized cytokine-secreting cells within an ectoparasite-induced inflammatory lesion and monitored the phenotype and cytokine profile of cells migrating from the inflammatory lesion to the local draining lymph node via the afferent lymphatics. Interleukin (IL)-8 producing cells were first detected in skin within 6 hr of infection, with increased numbers observed at 24 and 48 hr post infection. While these cells were concentrated within the neutrophil influx, adjacent to disrupted epidermis; they were also found scattered throughout the surrounding dermis in areas where significant cellular infiltration was not apparent. IL-1α- and IL-1β-producing cells could not be detected until 24 hr after infection and were restricted to areas of intense neutrophil accumulation. Concurrent with the onset of inflammation was a threefold increase in the total number of cells migrating through the draining afferent lymph. This increase in cellularity was due primarily to increased migration of CD4 and γδ T cells. Cytokine mRNA synthesis by migrating afferent lymph cells was 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-1β and IL-8, but not IL-1α or IL-6 mRNA, was detected in migrating afferent lymph cells. Tumour necrosis factor (TNF)-α-specific mRNA was present in migrating afferent lymph cells at all time points both prior to, and following infection. Soluble IL-8 protein, but not IL-1α, IL-1β or TNF-α protein, could be detected in lymph, with the amount of IL-8 detected increasing as the infection progressed. mRNA coding for cytokines associated with T-cell activation, such as IL-2, IL-4 or interferon (IFN)-γ, was also detected in migrating cells, although the cytokine profiles of different experimental animals were extremely variable.