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Adjuvant properties of a biocompatible thermo-responsive polymer of N-isopropylacrylamide in autoimmunity and arthritis
Indian Institute of Technology Kanpur, Kanpur, India.
Indian Institute of Technology Kanpur, Kanpur, India.
Karolinska Institute, Stockholm, Sweden.ORCID iD: 0000-0001-7790-8197
2011 (English)In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 8, no 65, p. 1748-1759Article in journal (Refereed) Published
Abstract [en]

To evaluate the thermo-responsive poly(N-isopropylacrylamide) (PNiPAAm) polymer as an adjuvant, we synthesized PNiPAAm through free radical polymerization and characterized it both in vitro and in vivo. The polymer when mixed with collagen type II (CII) induced antigen-specific autoimmunity and arthritis. Mice immunized with PNiPAAm-CII developed significant levels of CII-specific IgG response comprising major IgG subclasses. Antigen-specific cellular recall response was also enhanced in these mice, while negligible level of IFN-gamma was detected in splenocyte cultures, in vitro. PNiPAAm-CII-immunized arthritic mouse paws showed massive infiltration of immune cells and extensive damage to cartilage and bone. As determined by immunostaining, most of the CII protein retained its native configuration after injecting it with PNiPAAm in naive mice. Physical adsorption of CII and the high-molecular-weight form of moderately hydrophobic PNiPAAm induced a significant anti-CII antibody response. Similar to CII, mice immunized with PNiPAAm and ovalbumin (PNiPAAm-Ova) induced significant anti-ovalbumin antibody response. Comparable levels of serum IFN-gamma, IL-1beta and IL-17 were observed in ovalbumin-immunized mice with complete Freund, incomplete Freund (CFA and IFA) or PNiPAAm adjuvants. However, serum IL-4 levels were significantly higher in PNiPAAm-Ova and CFA-Ova groups compared with the IFA-Ova group. Thus, we show for the first time, biocompatible and biodegradable thermo-responsive PNiPAAm can be used as an adjuvant in several immunological applications as well as in better understanding of the autoimmune responses against self-proteins. © 2011 The Royal Society

Place, publisher, year, edition, pages
London: The Royal Society Publishing , 2011. Vol. 8, no 65, p. 1748-1759
Keywords [en]
Arthritis, Autoimmunity, Biocompatibility, Collagen, Thermo-responsive polymer
National Category
Biomaterials Science
Identifiers
URN: urn:nbn:se:hh:diva-48868DOI: 10.1098/rsif.2011.0114ISI: 000296578400007PubMedID: 21543351Scopus ID: 2-s2.0-80055005618OAI: oai:DiVA.org:hh-48868DiVA, id: diva2:1718807
Note

Funding text: We thank Prof. Rikard Holmdahl for support and encouragement. We are grateful to Carlos and Kristina Palestro for taking care of the animals. The following foundations provided financial support: Alex and Eva Wallstrom, Professor Nanna Svartz, Ake Wieberg, Anne Greta Holger Crafoord, KI (Fobi), Swedish Rheumatism Association, King Gustaf V:s 80-years Foundation and Swedish Research Council, VR-Link (2008-6007) and VR-project grant (2009-2338). A.K.S. acknowledges the senior research fellowship (SRF) from Council of Scientific and Industrial Research, India.

Available from: 2022-12-13 Created: 2022-12-13 Last updated: 2023-02-20Bibliographically approved

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Nandakumar, Kutty Selva

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