Early-life inflammation can have long lasting impact on pain processing and pain behaviours. For example, we have shown neonatal inflammation can result in changes within spinal neuronal networks and altered flinching of the hind paw 5 following formalin injection three weeks later. This suggests mechanisms for altered pain behaviours lie in first and second order neurons in the pain neuroaxis. Exactly how these changes progress during postnatal development is not known. Accordingly, we investigated neuroinflammatory markers in sensory neurons (dorsal root ganglia; DRGs) and spinal cords of Wistar rats (both sexes) after 10 early life inflammation. Rats were injected with LPS or saline on postnatal days (P) 3 and 5. DRGs and spinal cords (SC) were isolated on P7, 13 and 21, and the expression of six inflammatory mediators were quantified via RT-qPCR. In the DRG, four proinflammatory mediators were elevated in P7 rats exposed to LPS. By P13, only two proinflammatory agents were elevated, whereas at P21 the levels of all six inflammatory mediators were 15 similar between LPS and saline-treated rats. There were no sex-specific differences in the expression profile of any mediator in DRGs. In the spinal cord this expression profile was reversed with no change in inflammatory mediators at P7, elevation of two at P13 and four at P21 in LPS treated rats. Interestingly, these differences were greater in the spinal cords of female rats, indicating sex-specific modulation of neuroinflammation even at these early 20 stages of postnatal development. The increased inflammatory mediator profile in the spinal cords of P21 LPS-treated rats was accompanied by sex-specific modulation of astrocytic (GFAP) activation, with females showing an increase and males a decrease in GFAP following LPS exposure. Together, these data indicate sensory neurons are more susceptible to acute inflammation whereas inflammation in the spinal cord is delayed. The sex-specific 25 modulation of inflammation during critical phases of development may help explain altered pain behaviours in adult males and females.

SUMMARYIn reactive arthritis (ReA) a specific T cell response to the triggering bacterial antigen is present in the synovial fluid, while in paired peripheral blood T cells the response is tnarkedly reduced. The proliferative response to ReA-associated bacteria in the peripheral blood of ReA patients was compared with that seen in the blood of healthy adults, who denied exposure to these mierobes. and in the umbilical cord blood of newborns, who have clearly not been exposed to bacterial antigen. Peripheral blood mononuelear cells (PBMC) from non-exposed adults and those from umbilical cord blood proliferated to ReA-associated bacteria, whilst little response was seen in ReA PBMC. The response was MHC class Il-restricted, required processing of the bacterial antigen, was seen in both CD45RO ' and CD45RA^ subsets, and was not oligoclonal. These T cell responses are similar to (hose previously demonstrated in non-exposed individuals to malaria, leishmania and trypanosoma antigen, and may reflect the existence of "naiural* T ceil immunity to ReA-associated bacteria. The lack of such responses in ReA peripheral blood may suggest that such 'natural' responses may restrict the dissemination or progression of infection.

SummaryA double‐blind comparative study between 1 % hydrocortisone cream and a combination of 1% hydrocortisone cream and 2% miconazole cream has highlighted some of the problems with this type of research in general practice. The collection of adequate patient numbers within a predefined time scale proved a major problem. However, the study demonstrated the safety and efficacy of both these preparations in the treatment of intertrigo.

Early life inflammation has been linked to long-term deficits in the central nervous system in relation to behavioural disorders, but it is now becoming more apparent it can also lead to autonomic dysfunction. The brainstem contains all critical control centres for autonomic homeostasis, so we used the well-established model of neonatal lipopolysaccharide (LPS) exposure to examine the immediate and long-term impacts of systemic inflammation on the autonomic regions of the brainstem. Wistar rats were injected with LPS or saline on postnatal days 3 and 5, with sacrifices made on postnatal days 7 and 90. At both timepoints inflammatory mediators were assessed in the brainstem via RT-qPCR and microglia were characterised by immunofluorescence in the autonomic regions of the brainstem. In the brainstem there was a distinct sex-specific response of all measured inflammatory mediators at both ages, as well as significant neonatal sex differences in inflammatory mediators at baseline. AT both ages, microglial morphology had a significant change to branch length and soma size in a sex-specific manner, which strongly indicate a significant effect of neonatal immune activation. This data not only highlights the strong sex-specific response of neonates to LPS administration, but also the significant impact on the brainstem in adulthood.