CYTOKINE MESSENGER-RNA PROFILES IN CONTUSED SPINAL-CORD AND AXOTOMIZED FACIAL NUCLEUS SUGGEST A BENEFICIAL ROLE FOR INFLAMMATION AND GLIOSIS

We have studied temporal mRNA expression patterns for interleukin-1 be ta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF), and transformin g growth factor-beta 1 (TGF-beta 1) in two rat injury paradigms with v ery different cellular inflammatory reactions: contussion of the spina l cord and axotomy of the facial nerve. Our comparative analyses using semiquantitative reverse transcription polymerase chain reaction (RT- PCR) show an early and robust upregulation of IL-1 beta, TNF-alpha, IL -6, and M-CSF mRNAs in spinal cord after contusion injury. Peak expres sion of these mRNAs was transient and returned to control levels by 24 h postinjury. In contrast, expression of IL-1 beta and TNF-alpha mRNA s in the axotomized facial nucleus was minimal and delayed, and levels of M-CSF mRNA remained unaltered. Similar to injured spinal cord, the axotomized nucleus showed a dramatic and early upregulation of IL-6 m RNA but unlike spinal cord, IL-6 mRNA levels subsided only gradually. Both injury paradigms showed gradually increasing levels of TGF-beta 1 mRNA which were maximal at 7 days postinjury. RT-PCR analyses were al so performed on isolated blood-borne mononuclear cells and neutrophils . The results showed that these cells contain high levels of IL-1 beta and M-CSF mRNAs, moderate levels of TGF-beta and TNF-alpha mRNAs, and minimal levels of IL-6 mRNA The RT-PCR analyses together with histolo gical observations indicate that expression of the proinflammatory cyt okines IL-1 beta, TNF-alpha, and IL-6 is short-lived and self-limited after contusion injury, and that it occurs primarily within endogenous glial cells. Transient expression of these molecules likely triggers secondary events which may be beneficial to wound repair and regenerat ion. (C) 1998 Academic Press.