Interleukin 1 Trials in Cancer Patients: A Review of the Toxicity, Antitumor and Hematopoietic Effects

Abstract

Clinical trials of interleukin 1α (IL-1α) and IL-1βhave been completed that assess the toxicities of these cytokines as well as their hematopoietic and antitumor effects. Both forms of IL-1 recognize the same cell surface receptors and have similar toxicities and similar biological activities. Toxicities including fever, flu-like symptoms and dose-limiting hypotension can be severe yet manageable, and IL-1 can be given safely to human cancer patients. Most toxicities and biological effects appear to be dose-related. IL-1 alone has little antitumor activity against melanoma, renal cell carcinomas or other malignancies. The hematopoietic effects, including megakaryocytopoietic effects, are modest and are probably not worth the toxicity necessary to achieve them. However, IL-1 seems to endow certain progenitor cells with responsiveness to other hematopoietic cytokines including colony-stimulating factors and IL-3. One potential application of IL-1 is to help expand bone marrow ex vivo following stem cell harvest, which could allow further chemotherapy dose escalations in chemotherapy-sensitive tumors.

Tumour inflammasome‐derived IL‐1β recruits neutrophils and improves local recurrence‐free survival in EBV‐induced nasopharyngeal carcinoma

“…Nonetheless, we provide strong evidence that the chemoradiotherapeutic activation of the NLRP3 and AIM2 inflammasomes, via cathepsin B and ROS, is likely to emerge as a crucial player in the regulation of cancer immunotherapy. Compared with the results of clinical trials showing that IL‐1β treatment through intravenous infusion and subcutaneous administration effectively increases the level of peripheral neutrophils in cancer patients (Veltri & Smith, 1996), our findings show that manipulating tumour‐derived IL‐1β by chemoradiotherapy to induce N1 TANs should be considered as a strategy for improving immunotherapy, and that inflammasomes are promising therapeutic targets in cancers.…”

Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia

“…In this respect, human adipose tissue was found to produce and release pro‐inflammatory cytokines and chemokines including interleukin‐6 (9), tumor necrosis factor‐ α (10–12), interleukin‐1 (13), and interleukin‐8 (14). These cytokines and chemokines can induce neutrophilia via demargination of intravascular neutrophils, acceleration of bone marrow neutrophil release or enhancement of bone marrow granulopoiesis (15–19). Furthermore, leptin the anti‐obesity hormone, mostly produced in adipose tissue was shown to stimulate stem cells and produce granulocyte–macrophage colonies (20, 21).…”

Correlation of Local Interleukin‐1beta Levels with Specific IgA Response Against Gardnerella vaginalis Cytolysin in Women with Bacterial Vaginosis

“…Also other vaginal pathogens, not considered responsible for HIV risk elevation as Staphylococcus aureus 32 Candida albicans 33 are able to induce IL‐1. IL‐1 is a key mediator of the series of host responses to infection 27 , 34 , 35 and its therapeutic administration has been proposed 27 , 36–38 . Very recently IL‐18, which is a cytokine member of the IL‐1 family able to induce IL‐1beta and required for generating the Th1‐type response, was demonstrated to inhibit HIV‐1 production in PBMC 39 …”