The Determination of the Minimum Safe Level of Interleukin 10IL—10 in (3)
Recombinant human IL-10 (rHuIL-10) was produced for patients who have Crohn's disease and rheumatoid arthritisreact favorably towards treatment with recombinant IL-10-producing bacteria(11).However， rHuIL-10 treatment showed little efficiency for either Crohn's disease or rheumatoid arthritis' treatment(12).Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo(12).
In addition，PEGylated recombinant human IL-10 (PEG-rHuIL-10， AM0010) is now developing.A phase I clinical trial have been conducted and showed thatAM0010 led to systemic immune activation with elevated immune-stimulatory cytokines(IFNγ， IL-18， IL-7， GM-CSF and IL-4) and reduced transforming growth factor beta in the serum. Partial responses were observed in onepatient with uveal melanoma and four of 15 evaluable patients with RCC treated at 20 mg/kg (overall response rate， 27%). Prolonged stable disease of at least 4 months was observed in four patients，including one with colorectal cancer with disease stabilization for 20 months(13). These experiments proved that although IL-10 is immunosuppressive in bacteria-related infections， rHuIL-10/PEG-rHuIL-10 is mainly immunostimulatory in tumor treatment.
, 百拇医药
However， while the development of recombined IL-10 medicine made some progress， the development of the inhibitor of IL-10 is largely overlooked.IL-10 has beenreported to limit the protective immune response to M. tuberculosis infection， contributing to increased susceptibility to TB in a 2011 experiment(14). Inhumans， active TB correlates with increased levels of IL-10 (15-17). Compared with healthy controls， IL-10 has been shown to be elevated in the pleural fluid (17)，bronchoalveolar lavage fluid (BALF)(16)， sputum (17)， and serum(15) of patients with active pulmonary TB (PTB).In addition， In humans， in contrast to healthy controls， monocytes isolatedfrom PTB patients produce higher levels ofIL-10 (18).
, 百拇医药
Moreover， this overload of IL-10 in PTB patients results in immunocompromise when fighting Mtb. It has been showed that T cell proliferationand IFN-g productionfrom BALF obtained from PTB patients have been shown to be impaired in response to Mtb stimulation by endogenousIL-10(19). Production of IL-10 by human macrophages infected withM. tuberculosis has also been shown to inhibit phagosome maturation， resulting in impaired bacterial clearance(20).In addition， It is showed that the blockage of IL-10 signaling when injecting BCG may enhance the efficacy of the BCG(21)., 百拇医药(ChangTai. Li)
In addition，PEGylated recombinant human IL-10 (PEG-rHuIL-10， AM0010) is now developing.A phase I clinical trial have been conducted and showed thatAM0010 led to systemic immune activation with elevated immune-stimulatory cytokines(IFNγ， IL-18， IL-7， GM-CSF and IL-4) and reduced transforming growth factor beta in the serum. Partial responses were observed in onepatient with uveal melanoma and four of 15 evaluable patients with RCC treated at 20 mg/kg (overall response rate， 27%). Prolonged stable disease of at least 4 months was observed in four patients，including one with colorectal cancer with disease stabilization for 20 months(13). These experiments proved that although IL-10 is immunosuppressive in bacteria-related infections， rHuIL-10/PEG-rHuIL-10 is mainly immunostimulatory in tumor treatment.
, 百拇医药
However， while the development of recombined IL-10 medicine made some progress， the development of the inhibitor of IL-10 is largely overlooked.IL-10 has beenreported to limit the protective immune response to M. tuberculosis infection， contributing to increased susceptibility to TB in a 2011 experiment(14). Inhumans， active TB correlates with increased levels of IL-10 (15-17). Compared with healthy controls， IL-10 has been shown to be elevated in the pleural fluid (17)，bronchoalveolar lavage fluid (BALF)(16)， sputum (17)， and serum(15) of patients with active pulmonary TB (PTB).In addition， In humans， in contrast to healthy controls， monocytes isolatedfrom PTB patients produce higher levels ofIL-10 (18).
, 百拇医药
Moreover， this overload of IL-10 in PTB patients results in immunocompromise when fighting Mtb. It has been showed that T cell proliferationand IFN-g productionfrom BALF obtained from PTB patients have been shown to be impaired in response to Mtb stimulation by endogenousIL-10(19). Production of IL-10 by human macrophages infected withM. tuberculosis has also been shown to inhibit phagosome maturation， resulting in impaired bacterial clearance(20).In addition， It is showed that the blockage of IL-10 signaling when injecting BCG may enhance the efficacy of the BCG(21)., 百拇医药(ChangTai. Li)