Osteoimmunology of tumor necrosis factor-alpha, IL-6, and RANTES/CCL5: a review of known and poorly understood inflammatory patterns in osteonecrosis

Background: The immune and bone systems are closely linked via cytokine cross-talk. This interdisciplinary field of research is referred to as osteoimmunology and pertains to inflammatory and osteoarticular diseases that feature the primary expression of tumor necrosis factor-alpha (TNF-alpha) and IL-6. Objective: Are there bone resorptive processes wherein chronic inflammatory conditions are not linked to TNF-alpha and IL-6 expression, but rather to the expression of other cytokines? Materials and methods: A comprehensive literature search was performed in PubMed Central. Discussion: Although all diseases with cytokines involved in bone resorption (TNF-alpha and IL-6) are at the forefront of destructive inflammatory processes, there is one exception in the literature: fatty oxide osteoporosis/osteolysis in the jawbone (FDOJ), which is associated with significant bone softening. However, it should be noted that TNF-alpha and IL-6 fall below the levels found in a healthy jawbone in this condition. Another conspicuous finding is that there is a nearly 35-fold overexpression of the chemokine RANTES/CCL5 (R/C) in all FDOJ cases studied thus far in the literature. Conclusion: FDOJ appears to represent a unique cytokine and inflammatory pattern from osteolysis in the body. R/C can be defined as the dominant carrier of a maxillomandibular osteoimmunology.