Cytokine networking of innate immunity cells: a potential target of therapy

Abstract

Innate immune cells, particularly macrophages and epithelial cells, play a key role in multiple layers of immune responses. Alarmins and pro-inflammatory cytokines from the IL (interleukin)-1 and TNF (tumour necrosis factor) families initiate the cascade of events by inducing chemokine release from bystander cells and by the up-regulation of adhesion molecules required for transendothelial trafficking of immune cells. Furthermore, innate cytokines produced by dendritic cells, macrophages, epithelial cells and innate lymphoid cells seem to play a critical role in polarization of helper T-cell cytokine profiles into specific subsets of Th1/Th2/Th17 effector cells or regulatory T-cells. Lastly, the innate immune system down-regulates effector mechanisms and restores homoeostasis in injured tissue via cytokines from the IL-10 and TGF (transforming growth factor) families mainly released from macrophages, preferentially the M2 subset, which have a capacity to induce regulatory T-cells, inhibit the production of pro-inflammatory cytokines and induce healing of the tissue by regulating extracellular matrix protein deposition and angiogenesis. Cytokines produced by innate immune cells represent an attractive target for therapeutic intervention, and multiple molecules are currently being tested clinically in patients with inflammatory bowel disease, rheumatoid arthritis, systemic diseases, autoinflammatory syndromes, fibrosing processes or malignancies. In addition to the already widely used blockers of TNFα and the tested inhibitors of IL-1 and IL-6, multiple therapeutic molecules are currently in clinical trials targeting TNF-related molecules [APRIL (a proliferation-inducing ligand) and BAFF (B-cell-activating factor belonging to the TNF family)], chemokine receptors, IL-17, TGFβ and other cytokines.

Immunomodulatory effects of inosine pranobex on cytokine production by human lymphocytes

“…The order, amount and rate of cytokine production, both in vivo and in vitro, are characteristic of each individual cytokine and result from cross-regulatory interactions be- tween cytokines, the strength of the stimulus and other factors (13,16,17). The type of cytokines as well as the sequence of their production in our studies were similar to those reported by other authors (14).…”

Docosapentaenoic Acid (22:5n-3) Downregulates mRNA Expression of Pro-inflammatory Factors in LPS-activated Murine Macrophage Like RAW264.7 Cells

“…Chronic low-grade inflammation has been identified as the primary trigger for the pathogenesis of metabolic syndrome, cardiovascular diseases and cancers 13 15 . During the development of inflammation, production of pro-inflammatory cytokines and chemokines such as interleukin IL -1β, IL-6, monocyte chemoattractant protein-1 MCP-1 and regulated on the activation of normal T-cell expressed and secreted RANTES increases due to immune cell activation 16,17 . Macrophages play a crucial role in the regulation and production of cytokines and chemokines 18 .…”

Fractionated Trapa japonica Extracts Inhibit ROS-induced Skin Inflammation in HaCaT keratinocytes

“…자외선 자극에 의해 염증성 사이토카인의 농도가 높아진 피부 조직은 염증세포들을 유인하여 손상된 세포를 제거하고 회복시킨다 [4]. 이러한 과정에서 염 증세포는 손상받은 조직이나 세포를 제거하기 위해 염증 유발 사이토카인과 염증 매개인자와 같은 다양 한 물질들을 분비한다 [5][6][7][8]. 이와 같이 염증반응은 자 외선을 비롯한 외부 자극으로부터 인체를 보호하는 중요한 역할을 하지만 이러한 과정이 반복되거나 정 도가 과도할 경우 피부에 2차적인 손상을 입힐 수 있 다.…”