Immune Status of Individuals with Traumatic Spinal Cord Injury: A Systematic Review and Meta-Analysis

Abstract

Individuals with spinal cord injury (SCI) have higher infection rates compared to those without SCI. In this review, the immune status difference between individuals with and without traumatic SCI is investigated by examining their peripheral immune cells and markers. PubMed, Cochrane, EMBASE, and Ovid MEDLINE were searched without language or date restrictions. Studies reporting peripheral immune markers' concentration and changes in functional capabilities of immune cells that compared individuals with and without SCI were included. Studies with participants with active infection, immune disease, and central nervous system (CNS) immune markers were excluded. The review followed the PRISMA guidelines. Effect estimates were measured by Weighted Mean Difference (WMD) using a random-effects model. Study quality was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool. Fifty-four studies (1813 with SCI and 1378 without SCI) contributed to the meta-analysis. Leukocytes (n = 23, WMD 0.78, 95% CI 0.17; 1.38, I² 83%), neutrophils (n = 11, WMD 0.76, 95% CI 0.09; 1.42, I² 89%), C-reactive protein (CRP) (n = 12, WMD 2.25, 95% CI 1.14; 3.56, I² 95%), and IL6 (n = 13, WMD 2.33, 95% CI 1.20; 3.49, I² 97%) were higher in individuals with SCI vs. without SCI. Clinical factors (phase of injury, completeness of injury, sympathetic innervation impairment, age, sex) and study-related factors (sample size, study design, and serum vs. plasma) partially explained heterogeneity. Immune cells exhibited lower functional capability in individuals with SCI vs. those without SCI. Most studies (75.6%) had a moderate risk of bias. The immune status of individuals with SCI differs from those without SCI and is clinically influenced by the phase of injury, completeness of injury, sympathetic innervation impairment, age, and sex. These results provide information that is vital for monitoring and management strategies to effectively improve the immune status of individuals with SCI.

Keywords: immune depression; immunology; meta-analysis; traumatic spinal cord injury.

Figure 1

PRISMA flow diagram of included studies.

Figure 2

The pathophysiological process involved in SCI-IDS as captured in this systematic review. At the acute–subacute phase, the immune status is mainly driven by the injury with recruitment of leukocytes primarily by neutrophils and monocytes with higher release of inflammatory cytokines that direct the immune cells. Upon resolution of the lesion site inflammation, there is persistence of low-grade inflammation and higher levels of circulating leukocytes, particularly neutrophils. This is secondary to (1) the loss of sympathetic innervation in immune-related organs, (2) exposure of the immune cells to hormone imbalance, particularly to cortisol and norepinephrine, and (3) the membrane disruptions and tissue remodeling after loss of innervation as seen in higher cytokines and immune cells in previously selectively permeable or impermeable membranes (e.g., like in the testis) or increased activity of mucosal immune cells with decreased expression of junction proteins in the urothelium. Legend: a—greater splanchnic nerve; b—lesser splanchnic nerve; c—celiac ganglion; d—inferior mesenteric ganglion; f—spleen; e—adrenal glands; g—sympathetic nerves depending on the bone marrow site; ↓ significantly lower in SCI vs without SCI, ↑ significantly higher in SCI vs without SCI, ↔ no significant difference in SCI vs without SCI.