Purpose To investigate the prevalence of infected herniated nucleus material in lumbar disc herniations and to determine if patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone oedema) in the adjacent vertebrae after the disc herniation. MCs (bone oedema) in vertebrae are observed in 6 % of the general population and in 35-40 % of people with low back pain. These changes are strongly associated with low back pain. There are probably a mechanical cause and an infective cause that causes MC. Several studies on nuclear tissue from herniated discs have demonstrated the presence of low virulent anaerobic microorganisms, predominantly Propionibacterium acnes, in 7-53 % of patients. At the time of a herniation these low virulent anaerobic bacteria may enter the disc and give rise to an insidious infection. Local inflammation in the adjacent bone may be a secondary effect due to cytokine and propionic acid production. Methods Patients undergoing primary surgery at a single spinal level for lumbar disc herniation with an MRI-confirmed lumbar disc herniation, where the annular fibres were penetrated by visible nuclear tissue, had the nucleus material removed. Stringent antiseptic sterile protocols were followed. Results Sixty-one patients were included, mean age 46.4 years (SD 9.7), 27 % female. All patients were immunocompetent. No patient had received a previous epidural steroid injection or undergone previous back surgery. In total, microbiological cultures were positive in 28 (46 %) patients. Anaerobic cultures were positive in 26 (43 %) patients, and of these 4 (7 %) had dual microbial infections, containing both one aerobic and one anaerobic culture. No tissue specimens had more than two types of bacteria identified. Two (3 %) cultures only had aerobic bacteria isolated. In the discs with a nucleus with anaerobic bacteria, 80 % developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of those with aerobic bacteria and only 44 % of patients with negative cultures developed new MC. The association between an anaerobic culture and new MCs is highly statistically significant (P = 0.0038), with an odds ratio of 5.60 (95 % CI 1.51-21.95). Conclusion These findings support the theory that the occurrence of MCs Type 1 in the vertebrae adjacent to a previously herniated disc may be due to oedema surrounding an infected disc. The discs infected with anaerobic bacteria were more likely (P \ 0.0038) to develop MCs in the adjacent vertebrae than those in which no bacteria were found or those in which aerobic bacteria were found.

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Residues in human leukemia inhibitory factor (hLIF) crucial for binding to both the human LIF receptor (R) and gp130 were identified by analysis of alanine scanning mutants of hLIF in assays for both receptor binding and bioactivity. The region of hLIF most important for binding to the hLIF-R is composed of residues from the amino terminus of the D-helix, carboxyl terminus of the B-helix, and C-D loop. This site forms a distinct surface at the end of the four-helix bundle in the tertiary structure of the closely related murine LIF. The two residues of hLIF that contribute the majority of free energy for hLIF-R binding, Phe-156 and Lys-159 are surrounded by other residues which have only a moderate impact. This arrangement of a few key residues surrounded by less important ones is analogous to the functional binding epitope of human growth hormone for its receptor. A second region of hLIF that includes residues from the carboxyl terminus of the D-helix and A-B loop also had a weak influence on hLIF-R binding. Residues in hLIF from both the A-and C-helices are involved in binding the gp130 co-receptor. Abolition of the gp130 binding site in hLIF created antagonists of LIF action.Leukemia inhibitory factor (1-3) is a secreted cytokine that elicits pleiotropic effects on a diverse range of cell types, these include embryonic stem cells, primordial germ cells, neurons, adipocytes, hepatocytes, and osteoblasts (4, 5). In mice, gene knockout experiments have demonstrated that LIF 1 is essential for embryonic implantation (6, 7). In contrast to the mild phenotype in mice lacking the LIF gene, the targeted deficiency of the specific LIF receptor (LIF-R), results in mice that have multiple placental, skeletal, neural, and metabolic disorders, which cause perinatal death (8). The biological differences between these two genetic deficiencies is an outcome of the use of the LIF-R for signal transduction by several ligands. The cytokines known to bind to the LIF-R are included in a group that share some biological properties with LIF: oncostatin M, ciliary neurotrophic factor (CNTF), cardiotrophin (CT-1), interleukin-6 (IL-6), and interleukin-11 (9 -14).The crystal structure of recombinant murine LIF (mLIF) has been solved (15). LIF has a four ␣-helical bundle topology with up-up-down-down helix orientation that has long crossover loops between the first two and last two helices. The structure of LIF shows greatest homology to granulocyte-colony-stimulating factor (G-CSF; Ref. 16), human growth hormone (hGH; Ref. 17) and the recently determined CNTF (18). These proteins all belong to the hematopoietin cytokine family, which is characterized by the four-helix bundle structure, but limited sequence homology between family members (19 -21). The hematopoietin cytokine family is divided into the short and long chain subfamilies (21). The long chain group of which both LIF and hGH are members is characterized by helices of approximately 25 residues, the presence of short helical regions in the long loops, and the complete absence o...

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