Multi-vitamin supplementation blunts the circulating IL-6/IL-10 ratio increase after knee arthroplasty: A randomized, double-blind, placebo controlled study.

Circulating interleukin (IL)-6 and IL-10 concentrations can be elevated following the surgically induced trauma of total knee arthroplasty (TKA). An exaggerated increase in IL-6 relative to IL-10 (i.e., IL-6/IL-10 ratio) associates with trauma severity and indicative of pro-inflammatory predominance. Although various vitamins and minerals alter individual IL-6 and IL-10 concentrations in the blood, surprisingly, it is unknown if a multi-vitamin supplement alters the IL-6/IL-10 ratio during the systemic inflammatory response following TKA. The objective of this study was to identify if a multi-vitamin with mineral supplement taken prior to alters the circulating IL-6/IL-10 ratio following total knee arthroplasty (TKA). This study consisted of a randomized, double-blind, placebo controlled design. Twenty-one subjects undergoing elective, primary, unilateral TKA were randomly assigned to a placebo (PL, n = 11) or multi-vitamin with mineral supplement (MV, n = 10). Supplements were taken daily starting approximately 6-weeks prior to surgery. Supplements were not taken the day of surgery or during inpatient care 2-days after surgery. Circulating IL-6, IL-10, high-sensitivity CRP (hsCRP), vitamin C (ascorbic acid (AA)), vitamin D (25-hydroxyvitamin D (25(OH)D)), and vitamin E (α-tocopherol (αT)) concentrations were measured in fasting blood draw samples obtained ~6-weeks prior to surgery (and before starting supplementation), the morning of surgery, and 24-hours and 48-hours after surgery. MV supplementation tended to increase serum 25(OH)D and significantly increased plasma AA and plasma αT before surgery without mitigating the post-operative IL-6 and hsCRP increases. However, the post-operative increase in the serum IL-6/IL-10 ratio after surgery was significantly blunted in the MV group. Based on these findings, we conclude that a multi-vitamin with mineral supplement taken daily for several weeks before surgery might reduce the pro-inflammatory predominance after TKA. Future research confirming or refuting the novel data presented herein is needed.

Circulating IL-10 is compromised in patients predisposed to developing and in patients with severe knee osteoarthritis.

The purpose of this investigation was to identify if serum interleukin (IL)-10 and tumor necrosis factor (TNF)-α concentrations and their ratio (IL-10/TNF-α) are altered in subjects predisposed to developing knee osteoarthritis following ligamentous injury and in those with severe knee osteoarthritis. Serum IL-10 and TNF-α concentrations were measured in four groups of subjects (n = 218): (1) reportedly-healthy and non-injured control subjects (CON; n = 92), (2) subjects scheduled to undergo anterior cruciate ligament surgery (ACL; n = 42), (3) non-surgical subjects with knee osteoarthritis (OA; n = 60), and (4) subjects with knee osteoarthritis scheduled to undergo total knee arthroplasty (TKA; n = 24). X-ray images were used to grade the severity of knee osteoarthritis. Serum IL-10 and the serum IL-10/TNF-α ratio were significantly lower while serum TNF-α was not significantly perturbed with severe compared to moderate knee osteoarthritis (i.e., Kellgren-Lawrence grade 4 vs. 3, respectively). Serum IL-10 was significantly lower in the absence of serum TNF-α alterations in the ACL group. We conclude that serum IL-10 concentrations are compromised in subjects predisposed to developing knee osteoarthritis following ligamentous trauma and in subjects with radiographic evidence of severe knee osteoarthritis.

Is there a link between the neutrophil-to-lymphocyte ratio and venous thromboembolic events after knee arthroplasty? A pilot study.

BACKGROUND: This study aimed to identify (1) if the postoperative increase in the neutrophil-to-lymphocyte ratio (NLR) is different between contrasting knee arthroplasty procedures, and (2) if the NLR predicts venous thromboembolism (VTE) after total knee arthroplasty (TKA). MATERIALS AND METHODS: To address the first objective, we retrospectively studied patients who underwent primary unilateral TKA (n = 111) or unicompartmental knee arthroplasty (UKA; n = 74) between 2009 and 2012. Patients who required a blood transfusion, underwent autologous blood salvage, experienced any postoperative complication (such as VTE), or were re-admitted >90 days were excluded from analysis. For the second objective, we retrospectively identified patients (cases, n = 10) who underwent primary unilateral TKA between 2010 and 2012 and developed postoperative VTE (deep venous thrombosis, pulmonary embolism, or both) during inpatient care (postoperative day 1 or day 2). Cases were matched to surgeon, gender, body mass index, age, and date of surgery controls (n = 20) who underwent primary unilateral TKA without developing VTE before patient discharge. The NLR was calculated from the neutrophil and lymphocyte counts extracted from pre- and postoperative (day 1 and day 2) blood chemistry records. RESULTS: On postoperative day 1, the NLR increase was exacerbated (p = 0.02) following TKA compared to UKA and predicted (p = 0.02) the occurrence of VTE in TKA patients prior to hospital discharge. CONCLUSION: We conclude that the NLR increase is greater following TKA compared to UKA and could serve as a matrix to predict or identify a patient susceptible of sustaining VTE after TKA. LEVEL OF EVIDENCE: 3.

Vitamin D deficiency associates with γ-tocopherol and quadriceps weakness but not inflammatory cytokines in subjects with knee osteoarthritis.

Knee osteoarthritis (OA) is a degenerative joint condition and a leading cause of physical disability in the United States. Quadriceps weakness and inflammatory cytokines contribute to the pathogenesis of knee OA, and both of which, increase with vitamin D deficiency. Other micronutrients, such as vitamins C and E and ß-carotene, modulate inflammatory cytokines and decrease during inflammation. The purpose of this study was to test the hypothesis that vitamin D deficiency associates with quadriceps weakness, an increase in serum cytokines, and a decrease in circulating micronutrients in subjects with knee OA. Subjects (age, 48±1 y; serum 25(OH)D, 25.8±1.1 ng/mL) with knee OA were categorized as vitamin D deficient (n=17; serum 25(OH)D≤20 ng/mL), insufficient (n=21; serum 25(OH)D 20-29 ng/mL), or sufficient (n=18; serum 25(OH)D≥30 ng/mL). Single-leg strength (concentric knee extension-flexion contraction cycles at 60 °/s) and blood cytokine, carotene (α and ß), ascorbic acid, and tocopherol (α and γ) concentrations were measured. Quadriceps peak torque, average power, total work, and deceleration were significantly (all p<0.05) impaired with vitamin D deficiency. Serum γ-tocopherol concentrations were significantly (p<0.05) increased with vitamin D deficiency. In the vitamin D sufficient group, γ-tocopherol inversely correlated (r=-0.47, p<0.05) with TNF-α, suggesting a pro-inflammatory increase with a γ-tocopherol decrease despite a sufficient serum 25(OH)D concentration. We conclude that vitamin D deficiency is detrimental to quadriceps function, and in subjects with vitamin D sufficiency, γ-tocopherol could have an important anti-inflammatory role in a pathophysiological condition mediated by inflammation.