Analysis of cytokine profiles in sera of single and multiple infantile hemangioma

Abstract

Infantile hemangiomas (IH) are benign vascular tumors that are common in infancy. They vary in growth, size, location, and depth, and although most lesions are relatively small, approximately one fifth of patients have multiple lesions. Risk factors for IH include female sex, low birth weight, multiple gestation, preterm birth, progesterone therapy, and family history, but the mechanism that causes multiple lesions is unclear. We hypothesized that blood cytokines are involved as a cause of multiple IHs, and tried to prove this using sera and membrane arrays from patients with single and multiple IHs. Serum samples were obtained from five patients with multiple lesions and four patients with a single lesion, none of which had received any treatment. Serum levels of 20 cytokines were measured using human angiogenesis antibody membrane array. Four of the 20 cytokines (bFGF, IFN‐γ, IGF‐I, and TGF‐β1) were higher in the patients with multiple lesions than in those with single lesion, with statistically significant difference (p < 0.05). Notably, signal for IFN‐γ was evident in all cases with multiple IHs, but was absent in cases with single IH. Although not significant, there was mild correlation between IFN‐γ and IGF‐I (r = 0.64, p = 0.065), and between IGF‐I and TGF‐β1 (r = 0.63, p = 0.066). bFGF levels were strongly and significantly correlated with the number of lesions (r = 0.88, p = 0.0020). In conclusion, blood cytokines could act as a cause of multiple IHs. This is a pilot study with a small cohort, so further large‐scale studies are necessary.

Circulating Mesenchymal Stromal Cells in Patients with Infantile Hemangioma: Evaluation of Their Functional Capacity and Gene Expression Profile

“…The downregulation of TGFα gene expression in cMSCs of IH at T0 and its upregulation after propranolol therapy are not consensual with their proangiogenic activity. However, very recently, it has been reported both an inflammatory environment in IH with multiple lesions [40] and a role of inflammation in defining the paracrine profile of MSCs, possibly altering the expression of angiogenic cytokines such as TGFα, in favor of a major reparative capacity [41]. In addition, propranolol and its isomers have been described in in vitro studies to promote the internalization of the MSC membrane receptors binding either EGF or TGFα; a similar mechanism may alter in vivo the TGFα gene expression [42].…”

Analysis of infantile hemangioma without proliferation after birth

“…In addition to local triggers, multiple IHs appearing after birth may be caused by systemic factors, such as cytokines involved in systemic neovascularization or sensory nerve growth after birth. Actually, several cytokines (bFGF, IFN-γ, IGF-I, and TGF-β1) were higher in the patients with multiple lesions than in those with a single lesion, with statistically significant difference (11). The pathogenesis before involuting phase.…”