1.Immunomodulating activity of analogs of noninflammatory fragment 163-171 of human interleukin-1beta.
Bajpai K1, Singh VK, Sharan R, Yadav VS, Haq W, Mathur KB, Agarwal SS. Immunopharmacology. 1998 Jan;38(3):237-45.
The synthetic nonapeptide Val-Gln-Gly-Glu-Glu-Ser-Asn-Asp-Lys corresponding to the amino acid sequence 163-171 of human interleukin-1beta (IL-1beta) has been reported to retain considerable immunostimulatory activity of the native protein without the induction of the inflammatory or pyrogenic responses. Two lipophilic derivatives of this nonapeptide, one having a lauroyl residue (1) and the other having a palmitoyl residue (2) at the N-terminus of the peptide, and a more stable analog carrying D-Val residue at position 1 of the peptide (3) were synthesized with a view to find out if these structural modifications had a favorable effect on in vitro mouse thymocyte proliferation and IL-1 dependent inhibition of A375 cells. We have found that analogs (1) and (2) are active in both the tests like the parent nonapeptide. The lipophilic analog (2) is in fact, effective at a lower dose as compared to the parent nonapeptide in mouse thymocyte proliferation assay.
2.Construction of chimeric immunogens: Bioactive fragment of human IL-1β or polytuftsin (PT) capable of eliciting immune responses to HIV peptides.
Gokulan K1, Khare S, Rao DN. Indian J Clin Biochem. 1998 Jul;13(2):111-8. doi: 10.1007/BF02867872.
In this study, we have examined the effect of linking of bloactive fragment of human IL-1β (163-171) or polytuftsin (PT, a synthetic polymer of natural immunomodulator "tuftsin") with synthetic peptides of HIV on the induction of immune response to the synthetic peptides. A panel of synthetic peptides representing defined region of gp41, gp120 and gag were used as antigens. Immunomodulators linked peptides (i.e. peptide-IL-1β or peptide-PT) or peptide dimers were employed for immunization in Balb/c mice. Mice immunized with the peptide-immunomodulator develop effective T-cell proliferation,in vitro cytokine release and higher antibody production, but not with peptide dimers. We also found that peptide-immunomodulators induced high level of IgG2a antibody production. Furthermore, there was a positive correlation between the levels of cytokine (IL-2 & IFN-γ) and IgG isotype production. Thus it would appear that incorporation of IL-1β fragment or PT selectively enhances the Th1 type response to these peptides and may therefore be important for virus neutralization and clearance.
3.Comparison of human interleukin-1 beta and its 163-171 peptide in bone resorption and the immune response.
Lerner UH1, Ljunggren O, Dewhirst FE, Boraschi D. Cytokine. 1991 Mar;3(2):141-8.
Human interleukin-1 beta (IL-1 beta) caused a dose- and time-dependent enhancement of the release of 45Ca from prelabeled mouse calvaria in organ culture. In addition, IL-1 beta dose-dependently stimulated the formation of prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha in the calvarial bones. However, IL-1 beta-induced 45Ca release was only partially inhibited by blocking the PGE2 response with indomethacin, suggesting that enhanced PGE2 formation in response to IL-1 beta is not necessary to obtain a bone resorptive effect, but that prostaglandins potentiate the action of IL-1 beta. The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, administered simultaneously with antigen (SRBC) to C3H/HeN male mice, induced a dose-dependent enhancement of specific antibody-producing cells in the spleen (PFC). The degree of PFC stimulation was comparable to that caused by native human IL-1 beta. In mouse bone cultures, neither 45Ca release nor prostanoid formation was stimulated by fragment 163-171.
4.Enhancement of immune responses to the hepatitis B virus core protein through DNA vaccines with a DNA fragment encoding human IL-1beta 163-171 peptide.
Shao HJ1, Chen L, Shen MS, Yu GF. Acta Virol. 2003;47(4):217-21.
DNA vaccines have been widely used as effective means of eradicating a variety of viruses, parasites, bacteria as well as means of alleviating allergic and autoimmune diseases and tumors. As interleukin 1 (IL-1) plays an essential role in augmenting both cellular and humoral immune responses to foreign antigens, it may represent a good candidate for an adjuvant to DNA vaccines. Since the inflammatory activity of IL-1 may have a restricted application to DNA vaccines, we explored the possibility of augmenting immune response without unwanted inflammatory effect using IL-1beta 163-171 peptide, which is essential for IL-1 receptor 1 binding. A DNA fragment encoding the human IL-1beta 163-171 peptide of concern was fused to the Hepatitis B virus (HBV) core DNA vaccine, and injected into mice to analyze its immune responses. Compared with the control mice which received hepatitis B virus core antigen (HBcAg) alone, significant increase in not only the HBcAg-specific antibody response but also in T cell proliferation was observed in mice which received IL-1beta 163-171-HBcAg.
