Update on cytokines

doi:10.1016/S0091-6749(96)80146-1

Journal of Allergy and Clinical Immunology

Volume 97, Issue 3, March 1996, Pages 719-733

https://doi.org/10.1016/S0091-6749(96)80146-1 Get rights and content

Summary

Cytokines that are important in the pathophysiology of allergic disorders are summarized on Table V. The IgE isotype switch results from the activities of IL-4 and IL-13 and is inhibited by IFN-ggg and TGF-β. IL-2, IL-5, and IL-6 synergize with IL-4 and IL-13 to enhance IgE secretion. IL-4 is responsible for the differentiation of IL-4-producing lymphocytes, whereas IL-12 inhibits the differentiation of IL-4-producing T cells. IL-5 is the most important eosinophilopoietin, and together with GM-CSF and IL-3, prolongs the survival of and activates mature eosinophils. These three cytokines are responsible for the generation of the hypodense eosinophils which characterize the asthmatic state. Eosinophilia may also result from selective recruitment by the eosinophil chemotactic factors RANTES, MIP-1α, and eotaxin. Mast cell proliferation results from the activities of IL-3, IL-9, IL-10, nerve growth factor, and stem cell factor. Finally, several cytokines contribute to the inflammatory state of allergic disorders. IL-1, TNF, and IFN-γ increase expression of endothelial cell adhesion molecules and support the egress of mononuclear cells, neutrophils, and eosinophils into the lungs. Induction of vascular cell adhesion molecule-1 by IL-4 may promote the selective recruitment of eosinophils, basophils, and lymphocytes. Many cytokines may then contribute to the activation of these leukocytes once they have reached the airways.

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The other example is IL-1, which mediates various physiological responses, including inflammation and immunological reactions, and is implicated in the response to inflammation. IL-1β is a cytokine produced by monocytes and macrophages that are involved in the utilization of inflammatory cells and promote pro-inflammatory cytokine responses [1–2,4,20–21]. Sputum and BAL samples from CF patients who have been infected with P. aeruginosa for a long time show high levels of IL-1β.
Cytokines play a crucial role in the immune system's regulation by mediating protective responses to infections. anti-inflammatory and pro-inflammatory cytokines are in equilibrium. Therefore, any alteration in cytokine production or cytokine receptor expression might result in pathological illnesses and health issues. Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane regulator (CFTR) gene. Lung infection in these patients is related to chronic bacterial airway infection and inflammation, which is triggered by some inflammatory cytokines. Our goal was to compare the cytokine patterns in CF patient's serum and PBMCs caused by microbial pathogens that colonized their airways to controls.
ELISA and Real-time PCR were used to determine the levels of IL-10, IFN-γ, IL-4, TGF-β, IL-8, and IL-17 in serum and PBMC cells. Blood parameters in both patients and healthy people were studied.
An increase in IL-10, IFN-γ, IL-4 (p-v = 0.03, 0.024 and 0.003) levels and a decrease in IL-17 (p-v = 0.004) was found in Pseudomonas aeruginosa positive patients. There were no different in TGF-β and IL-8 (p-value = 0.778 and 0.903) in this patients. IL-10, IFN-γ, and IL-4 (p-value = 0.023, 0.001 and 0.002) levels were high in Staphylococcus aureus positive patients and TGF-β, IL-17, and IL-8 (p-value = 0.085, 0.167 and 0.362) were not significantly different in the patient and control groups. IFN-γ and IL-4 levels were higher in patients without infection who had normal microbiota (p-v = 0.002 and 0.024). In patients with P. aeruginosa, WBC and platelets increased, and MCH and MCV decreased. Patients with normal microbiota had less MCV.
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A new cycloartane sapogenol and a new cycloartane xyloside were isolated from Astragalus karjaginii BORISS along with thirteen known compounds. The structures of the new compounds were established as 3-oxo-6α,16β,24(S),25-tetrahydroxycycloartane (1) and 6-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (2) by 1D- and 2D-NMR experiments as well as ESIMS and HRMS analyses. The presence of the keto function at position 3 was reported for the first time for cyclocanthogenol sapogenin of Astragalus genus. In vitro immunomodulatory effects of the new compounds (1 and 2) along with the n-BuOH and MeOH extracts of A. karjaginii at two different doses (3 and 6 μg) were tested on human whole blood for in vitro cytokine release (IL-2, IL-17A and IFN-γ) and hemolytic activities. The results confirmed that compound 2, a monodesmosidic saponin, had the strongest effect on the induction of both IL-2 (6 μg, 6345.41 ± 0.12 pg/mL (× 5), P < 0.001) and a slight effect upon IL-17A (3 μg, 5217.85 ± 0.72 pg/mL, P < 0.05) cytokines compared to the other test compounds and positive controls (AST VII: Astragaloside VII; and QS-21: Quillaja saponin 21). All tested extracts and molecules also induced release of IFN-γ remarkably ranging between 5031.95 ± 0.05 pg/mL, P < 0.001 for MeOH extract (6 μg) and 5877.08 ± 0.06 pg/mL, P < 0.001 for compound 1 (6 μg) compared to QS-21 (6 μg, 5924.87 ± 0.1 pg/mL, P < 0.001). Administration of AST VII and other test compounds did not cause any hemolytic activity, whereas QS-21 resulted a noteworthy hemolysis.
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Phytochemical investigations on n-butanol extract of Cephalaria balansae Raus. (Caprifoliaceae) led to the isolation of four previously undescribed triterpenoid saponins based on hederagenin type aglycone, namely, balansoides A-D, along with ten known compounds. Their structures were proposed based on 1D and 2D NMR spectroscopic data, HRESIMS analysis and chemical evidence as 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl ester, 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-galactopyranosyl-(1 → 6)-β-D-glucopyranosyl ester and 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester. The four saponins were evaluated for their potential cytotoxic activity against HEK-293, A-549, HeLa cells and for hemolytic properties on human blood cells. Balansoide A displayed significant inhibitory effects on cancerous A-549 and HeLa cells, and non-cancerous HEK-293 cells with IC₅₀ values of 12, 15 and 8 μM, respectively. Balansoides A-D together with n-butanol extract exhibited considerable hemolysis in human erythrocyte cells. Immunomodulatory properties of balansoides A-D were also evaluated in activated whole blood cells by PMA plus ionomycin. While balansoides A-C increased IL-1β concentration with values of 1004.47, 991.57 and 966.50 pg/ml, only balansoide B augmented a slight IFN-γ secretion with value of 5219.14 pg/ml. None of the compounds changed IL-2 levels significantly.
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Update on cytokines

Summary

J Biol Chem

Cell

Immunol Today

Immunol Today

Blood

J Biol Chem

Adv Immunol

Immunol Today

Immunol Today

Immunol Today

Cell

Blood

Immunol Today

Cell

Immunol Today

Curr Opin Immunol

Cell

Blood

Blood

Cell

J Allergy Clin Immunol

CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein

Science

The biology of cachectin/TNF: a primary mediator of the host response

Annu Rev Immunol

Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization

Nucleic Acids Res

Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma

Science

Stimulation of neutrophils by tumor necrosis factor

J Immunol

Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia

Nature

The role of interleukin-1 in disease

N Engl J Med

Interleukin 1 signaling occurs exclusively via the type I receptor

The type II “receptor” as a decoy target for interleukin 1 in polymorphonuclear leukocytes: characterization of induction by dexamethasone and ligand binding properties of the released decoy receptor

J Exp Med

Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist

Nature

Studies on the molecular nature of human interleukin 1

J Immunol

Molecular cloning of the interleukin-1β converting enzyme

Science

A protein complex required for signal-sequence-specific sorting and translocation

Nature

Interleukin-1 receptor antagonist reduces mortality from endotoxin shock

Nature

Neutralization of endogenous IL-1 receptor antagonist exacerbates and prolongs inflammation in rabbit immune colitis

J Clin Invest

Interleukin 6: an overview

Annu Rev Immunol

Interleukin-6 in biology and medicine

Adv Immunol

Properties of the novel proinflammatory supergene “intercrine” cytokine family

Annu Rev Immunol

Neutrophil attractant/activation protein-1 (NAP-1 [Interleukin-8])

Am J Respir Cell Mol Biol

Interleukin-12

J Leukoc Biol

Dual stimulatory and inhibitory effect of NK cell stimulatory factor/IL-12 on human hematopoiesis

J Immunol

Utilization of the β chain and γ chains of the IL-2 receptor by the novel cytokine IL-15

EMBO J.

Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor

Science

Structure and expression of a cloned cDNA for human interleukin-2

Nature

Interleukin 2

Annu Rev Immunol

The IL-2 receptor complex: its structure, function, and target genes

Annu Rev Immunol

Molecular cloning and expression of cDNAs for the human interleukin-2 receptor

Nature

Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association

Science

Reconstitution of functional receptor for human interleukin-2 in mosue cells

Nature

Interaction of the IL-2 receptor with the src-family kinase p56^lck: identification of novel intermolecular association