This review has summarized recent information derived from many laboratories on the discovery, characteristics, and properties of a new member of the IL-1 family, IL-1 receptor antagonist. In addition to information, an emphasis has been placed on unanswered questions and new concepts. The existence of this first-described naturally occurring specific cytokine receptor antagonist may lead to a different perspective on the cytokine network. A major unanswered question emphasized throughout this review, that now can be addressed more directly, concerns what are the physiological roles of members of the IL-1 family. Although IL-1 beta is presumed to function primarily as an extracellular cytokine, this molecule lacks a leader peptide, is synthesized and handled by the cells in a manner suggestive of a cytoplasmic (not secretory) protein, and may only be released after cellular injury. Furthermore, although IL-1ra possesses a leader sequence, 50% or more of this protein remains cell associated. Do these observations suggest that members of the IL-1 family possess important intracellular functions, as yet undetermined? IL-1 alpha may play an intracellular role in regulating senescence; an IL-1 alpha antisense oligodeoxynucleotide was shown to prolong the life span of cultured human endothelial cells. Whether intracellular IL-1ra plays a role in influencing life span has not been determined. The discovery of IL-1ra has led to a first level of assumptions that this molecule may be functioning in vivo to regulate the pleiotropic extracellular effects of IL-1 in physiological or pathophysiological processes. Although enticing, these assumptions have not yet been proven to be true. Perhaps we need to look beyond, or within, and consider that IL-1ra and other members of the IL-1 family may have additional roles in normal or abnormal cell growth and development.
W P Arend
Title and authors | Publication | Year |
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Cytokine inhibition in the treatment of COPD
G Caramori, IM Adcock, AD Stefano, KF Chung |
International journal of chronic obstructive pulmonary disease | 2014 |
Vandetanib and indwelling pleural catheter for non-small cell lung cancer with recurrent malignant pleural effusion
E Massarelli, A Onn, EM Marom, CM Alden, DD Liu, HT Tran, B Mino, II Wistuba, SA Faiz, L Bashoura, GA Eapen, RC Morice, JJ Lee, WK Hong, RS Herbst, CA Jimenez |
Clinical Lung Cancer | 2014 |
Production of IL-1β by bone marrow-derived macrophages in response to chemotherapeutic drugs: Synergistic effects of doxorubicin and vincristine
J Wong, LT Tran, EA Magun, BE Magun, LJ Wood |
Cancer biology & therapy | 2014 |
Robust pro-inflammatory and lesser anti-inflammatory immune responses during primary simian varicella virus infection and reactivation in rhesus macaques
V Traina-Dorge, R Sanford, S James, LA Doyle-Meyers, E Haro, M Wellish, D Gilden, R Mahalingam |
Journal of Neurovirology | 2014 |
Stroke, IL-1ra, IL1RN, infection and outcome
KJ Becker, D Dankwa, R Lee, J Schulze, D Zierath, P Tanzi, K Cain, A Dressel, D Shibata, J Weinstein |
Neurocritical Care | 2014 |
Active systemic lupus erythematosus is associated with a reduced cytokine production by B cells in response to TLR9 stimulation
J Sieber, C Daridon, SJ Fleischer, V Fleischer, F Hiepe, T Alexander, G Heine, GR Burmester, S Fillatreau, T Dörner |
Arthritis Research & Therapy | 2014 |
Role of Cytokine Signaling in Group B Streptococcus -Stimulated Expression of Human Beta Defensin-2 in Human Extraplacental Membranes
E Boldenow, KA Hogan, MC Chames, DM Aronoff, C Xi, R Loch-Caruso |
American Journal of Reproductive Immunology | 2014 |
In vivo retention and bioactivity of IL-1ra microspheres in the rat intervertebral disc: a preliminary investigation
DJ Gorth, JT Martin, GR Dodge, DM Elliott, NR Malhotra, RL Mauck, LJ Smith |
Journal of Experimental Orthopaedics | 2014 |
Involvement of endogenous transforming growth factor-α in signal transduction pathway for interleukin-1β-induced hepatocyte proliferation
M Kimura, H Moteki, M Ogihara |
European Journal of Pharmacology | 2014 |
Predicting proliferative vitreoretinopathy: temporal and external validation of models based on genetic and clinical variables
J Rojas, I Fernandez, JC Pastor, RE MacLaren, Y Ramkissoon, S Harsum, DG Charteris, JC van Meurs, S Amarakoon, J Garcia-Arumi, JM Ruiz-Moreno, A Rocha-Sousa, M Brion, A Carracedo |
The British journal of ophthalmology | 2014 |
Follicular-phase ovarian follicular fluid and plasma cytokine profiling of natural cycle in vitro fertilization patients
NE Baskind, NM Orsi, V Sharma |
Fertility and Sterility | 2014 |
Reference Module in Biomedical Sciences
DL Sackett, RB Haynes |
2014 | |
Inflammation in Parkinson's Disease
M Thomas |
2014 |