| Summary: | <p>Preterm condition gives a new stressful environment to infants. This condition needs a good and gradual adaptation. External environmental conditions, treatment, care and good nutrition are needed. Massage stimulation in preterm infants is a method that can prepare preterm infants’ adaptation through the critical post-birth period. A good adaptation of the system will provide better organ homeostasis including the immune system.</p><p>There are three paths of mechanisms that can explain how massage stimulation can regulate pro-inflammatory cytokines TNF-α and IL-6. The first: the hypothalamus pathway, massage stimulation act as a comfort stimulation that can control (inhibit) the release of pro-inflammatory cytokines TNF-α and IL-6 by macrophages; second: through activation of vagus nerve, massage stimulation act as a tactile stimulation which activates vagal system and the immune system; third: the hypothalamic-pituitary pathway, massage stimulation act as a kinesthetic stimulation that activates the hypothalamic-pituitary to release cortisol, GH (Growth hormone) and IGF-1 (Insulin-like Growth Factor 1). A randomized controlled trial about massage stimulation on preterm infants was performed in Sanglah Hospital Denpasar on 2011. The study revealed a different level of cytokine pro-inflammation TNF-α (<em>p=</em>0.025) and IL-6 (<em>p=</em>0,001) comparing before and after condition massage stimulation. Outcome of body weight were also different at before and after massage stimulation, with <em>p value </em>0.042.</p><p>Mechanisms of massage stimulation affect the immune system of preterm infants through regulation of inhibition the release of pro-inflammatory cytokine TNF-α, IL-6 by macrophages, through three main pathways: the hypothalamic; activation of the vagus nerve and the hypothalamic-pituitary-adrenal axis.</p>
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