Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by several immunological abnormalities. The pathogenic importance of T cells in this disease is well established. Interleukin-16 (IL-16) is a cytokine which is mainly produced by CD8+ T cells and induces chemotaxis of CD4+ T cells and monocytes. IL-16 levels have been shown to be elevated in SLE patients in a cross-sectional study, but the mechanism is unknown. To explore whether the increased IL-16 levels are associated with genetic background or the disease itself, we investigated the IL-16 level in healthy first-degree family members of SLE patients and SLE patients who were followed over time with regard to disease activity. We observed high IL-16 levels in SLE patients with severe disease compared to SLE patients with non-severe disease and healthy controls. Furthermore, IL-16 levels in first-degree relatives were not different from those in healthy controls. These results suggest that high IL-16 levels are associated with severity of SLE, but not with genetic susceptibility to SLE. Finally, we followed the disease activity of SLE patients over time, which showed significant correlation between the SLE disease activity index and IL-16, ESR and the complement components C3, C4 and CH50. In conclusion, these results implicate an association of IL-16 with SLE.

Integrative Omics Approach Identifies Interleukin-16 as a Biomarker of Emphysema

“…This observation would tend to favor the ''British Hypothesis'' that asthma and COPD (in particular, emphysema) are distinct diagnoses as opposed to the Dutch hypothesis, which postulates that the two diseases are related through a continuum of airway inflammation (Barnes, 2006). Although the role that IL-16 might play in emphysema and COPD is unknown, one possibility is that it is ( Lard et al, 2002;Lee et al, 1998), rheumatoid arthritis (RA) (Blaschke et al, 2001;Lard et al, 2004); bullous pemphigoid (Frezzolini et al, 2004), diabetes (Meagher et al, 2010), and preeclampsia (Gu et al, 2008). In a mouse model of rheumatoid arthritis, IL-16 attenuates joint inflammation (Klimiuk et al, 1999).…”

“…In a mouse model of rheumatoid arthritis, IL-16 attenuates joint inflammation (Klimiuk et al, 1999). However, IL-16 plasma levels are elevated during RA and SLE flare-ups in humans, suggesting that IL-16 may play a regulatory role rather than a pathogenic role (Blaschke et al, 2001;Lard et al, 2002;Lee et al 1998). Adoptive transfer experiments of IL-16 expressing CD8 + (suppressor) cells result in a marked reduction of autoimmunity in rheumatoid synovitis (Klimiuk et al, 1999).…”

“…Both immune and non-immune cells produce IL-16, including T-cells, eosinophils, dendritic cells, fibroblasts, epithelial cells, and neuronal cells . Although IL-16 plasma levels have been associated with diverse diseases, such as AIDS ( Jin et al, 2009) and Alzheimer's disease (Motta et al, 2007), the majority of literature has focused on the role of IL-16 allergic, airways, and autoimmune diseases (Lard et al, 2002).…”

“…Furthermore, high systemic levels of IL-16 at the initial presentation of RA are associated with greater joint destruction (Lard et al, 2004). Serum IL-16 is also higher in systemic lupus erythematosus (SLE) patients compared to healthy controls (Lard et al, 2002;Lee et al, 1998). In RA and SLE, increases in IL-16 are associated with disease activity and thought to be mediated by CD4 + cells.…”

Chemokine Receptor CXCR3 Desensitization by IL-16/CD4 Signaling Is Dependent on CCR5 and Intact Membrane Cholesterol

“…Similar to many chemokines, IL-16 has been detected at sites of inflammation in various inflammatory conditions, such as asthma, inflammatory bowel disease, rheumatoid arthritis, delayed-type hypersensitivity, multiple sclerosis, systemic lupus erythematosus, and Graves' disease (11)(12)(13)(14)(15)(16)(17). The precise role of IL-16 in these diseases has yet to be determined; however, it has now been shown that the exogenous administration of IL-16 in a murine model of acute allergic airway inflammation results in significant attenuation of both airway hyper-reactivity and lung inflammation (18).…”